Cachectin/Tumor Necrosis Factor and Lymphotoxin

  • B. Beutler
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 95 / 2)


As it acts to eradicate viruses, bacteria, and parasitic pathogens, the host immune system may sometimes prove to be a liability rather than an asset. The inflammatory response to invasive organisms may injure the host as surely as the organisms themselves, and, in many instances, the immune response is itself a major pathogenetic vehicle. Thus, physicians strive to temper the immune response in their attempts to manage some infectious disease states. At present, this is achieved through the use of glucocorticosteroids and, occasionally, cytotoxic drugs.


Tumor Necrosis Factor Human Tumor Necrosis Factor Hemorrhagic Necrosis Recombinant Tumor Necrosis Factor Recombinant Human Tumor Necrosis Factor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Abbott J, Doyle PJ, Ngiam K, Olson CL (1981) Ontogeny of murine T lymphocytes. I. Maturation of thymocytes induced in vitro by tumor necrosis factor-positive serum (TNF+)1,2. Cell Immunol 57: 237–250PubMedGoogle Scholar
  2. Abe S, Gatanaga T, Yamazaki M, Soma G, Mizuno D (1985) Purification of rabbit tumor necrosis factor. FEBS Lett 180: 203–206PubMedGoogle Scholar
  3. Agarwal S, Drysdale B-E, Shin HS (1988) Tumor necrosis factor-mediated cytotoxicity involves ADP-ribosylation. J Immunol 140: 4187–4192PubMedGoogle Scholar
  4. Aggarwal BB, Kohr WJ, Hass PE, Moffat B, Spencer SA, Henzel WJ, Bringman TS, Nedwin GE, Goeddel DV, Harkins RN (1985a) Human tumor necrosis factor. Production, purification, and characterization. J Biol Chem 260: 2345–2354Google Scholar
  5. Aggarwal BB, Eessalu TE, Hass PE (1985b) Characterization of receptors for human tumour necrosis factor and their regulation by gamma-interferon. Nature 318: 665–667PubMedGoogle Scholar
  6. Aggarwal BB, Traquina PR, Eessalu TE (1986) Modulation of receptors and cytotoxic response of tumor necrosis factor-alpha by various lectins. J Biol Chem 261: 13652–13656PubMedGoogle Scholar
  7. Algire GH, Legallais FY, Anderson BF (1952) Vascular reactions of normal and malignant tissues in vivo. V. The role of hypotension in the action of a bacterial polysaccharide on tumors. JNCI 12: 1279–1295PubMedGoogle Scholar
  8. Atkinson YH, Marasco WA, Lopez AF, Vadas MA (1988) Recombinant human tumor necrosis factor-alpha: regulation of n-formylmethionylleucylphenylalanine receptor affinity and function on human neutrophils. J Clin Invest 81: 759–765PubMedGoogle Scholar
  9. Averbook B, Ulich T, Jeffes E, Yamamoto R, Chow G, Masunaka I, Granger G (1987) Human alpha lymphotoxin and TNF induce different types of inflammatory responses in normal tissue. Fed Proc 46 (3): 562Google Scholar
  10. Bachwich PR, Chensue SW, Larrick JW, Kunkel SL (1986) Tumor necrosis factor stimulates interleukin-1 and prostaglandin E2 production in resting macrophages. Biochem Biophys Res Commun 136: 94–101PubMedGoogle Scholar
  11. Balkwill F, Burke F, Talbot D, Tavernier J, Osborne R, Naylor S, Durbin H, Fiers W (1987) Evidence for tumour necrosis factor/cachectin production in cancer. Lancet 2 (8570): 1229–1232PubMedGoogle Scholar
  12. Bate CAW, Taverne J, Playfair JHL (1988) Malarial parasites induce TNF production by macrophages. Immunology 64: 227–231PubMedGoogle Scholar
  13. Bauss F, Droge W, Mannel DN (1987) Tumor necrosis factor mediates endotoxic effects in mice. Infect Immun 55: 1622–1625PubMedGoogle Scholar
  14. Behr SR, Kraemer FB (1986) Effects of activation on lipoprotein lipase secretion by macrophages. Evidence for autoregulation. J Exp Med 164: 1362–1367PubMedGoogle Scholar
  15. Berger M, Wetzler EM, Wallis RS (1988) Tumor necrosis factor is the major monocyte product that increases complement receptor expression on mature human neutrophils. Blood 71: 151–158PubMedGoogle Scholar
  16. Bermudez LEM, Young LS (1988) Tumor necrosis factor, alone or in combination with IL-2, but not IFN-gamma, is associated with macrophage killing of Mycobacterium avium complex. J Immunol 140: 3006–3013PubMedGoogle Scholar
  17. Bertini R, Bianchi M, Ghezzi P (1988) Adrenalectomy sensitizes mice to the lethal effects of interleukin 1 and tumor necrosis factor. J Exp Med 167: 1708–1712PubMedGoogle Scholar
  18. Bertolini DR, Nedwin G, Bringman T, Smith D, Mundy GR (1986) Stimulation of bone resorption and inhibition of bone formation in vitro by human tumour necrosis factor. Nature 319: 516–518PubMedGoogle Scholar
  19. Besedovsky H, del Rey A, Sorkin E, Dinarello CA (1986) Immunoregulatory feedback between interleukin-1 and glucocorticoid hormones. Science 233: 652–654PubMedGoogle Scholar
  20. Beutler B, Milsark IW, Cerami A (1985a) Passive immunization against cachec-tin/tumor necrosis factor ( TNF) protects mice from the lethal effect of endotoxin. Science 229: 869–871Google Scholar
  21. Beutler B, Milsark IW, Cerami A (1985b) Cachectin/tumor necrosis factor: production, distribution, and metabolic fate in vivo. J Immunol 135: 3972–3977PubMedGoogle Scholar
  22. Beutler B, Greenwald D, Hulmes JD, Chang M, Pan Y-CE, Mathison J, Ulevitch R, Cerami A (1985c) Identity of tumour necrosis factor and the macrophage-secreted factor cachectin. Nature 316: 552–554PubMedGoogle Scholar
  23. Beutler B, Mahoney J, Le Trang N, Pekala P, Cerami A (1985d) Purification of cachectin, a lipoprotein lipase-suppressing hormone secreted by endotoxin-induced RAW 264.7 cells. J Exp Med 161: 984–995PubMedGoogle Scholar
  24. Beutler B, Krochin N, Milsark IW, Luedke C, Cerami A (1986) Control of cachectin (tumor necrosis factor) synthesis: mechanisms of endotoxin resistance. Science 232: 977–980PubMedGoogle Scholar
  25. Beutler B, Thompson P, Keyes J, Hagerty K, Crawford D (1988) Assay of a ribonuclease that preferentially hydrolyses mRNA’s containing cytokine-derived UA-rich instability sequences. Biochem Biophys Res Commun 152: 973–980PubMedGoogle Scholar
  26. Beutler E, Gelbart T, Han J, Koziol J A, Beutler B (1988) Evolution of the genome and the genetic code: selection at the dinucleotide level by methylation and polyribonucleotide cleavage. Proc Natl Acad Sci USA 86: 192–196Google Scholar
  27. Blanchard DK, Djeu JY, Klein TW, Friedman H, Stewart WE II (1987) The induction of tumor necrosis factor (TNF) in murine lung tissue during infection with Legionella pneumophila: a potential protective role of TNF ( Abstr ). Lymphokine Res 6: 1421Google Scholar
  28. Blanchard DK, Djeu JY, Klein TW, Friedman H, Stewart WE II (1988) Protective effects of tumor necrosis factor in experimental Legionella pneumophila infections of mice via activation of PMN function. J Leukocyte Biol 43: 429–435PubMedGoogle Scholar
  29. Bloksma N, Hofhuis FM, Willers JM (1984) Role of mononuclear phagocyte function in endotoxin-induced tumor necrosis. Eur J Cancer Clin Oncol 20: 397–03PubMedGoogle Scholar
  30. Bomalaski JS, Chen M-J, Clark MA (1987) Induction of phospholipase A2 activity and synthesis of a phospholipase A2 activating protein (PLAP) by tumor necrosis factor. Arthritis Rheum 30:S28Google Scholar
  31. Brigham KL, Meyrick B (1984) Interactions of granulocytes with the lungs. Circ Res 54: 623–635Google Scholar
  32. Broudy VC, Harlan JM, Adamson JW (1987) Disparate effects of tumor necrosis factor-alpha/cachectin and tumor necrosis factor-beta/lymphotoxin on hematopoietic growth factor production and neutrophil adhesion molecule expression by cultured human endothelial cells. J Immunol 138: 4298–4302PubMedGoogle Scholar
  33. Caput D, Beutler B, Hartog K, Brown-Shimer S, Cerami A (1986) Identification of a common nucleotide sequence in the 3’-untranslated region of mRNA molecules specifying inflammatory mediators. Proc Natl Acad Sci USA 83: 1670–1674PubMedGoogle Scholar
  34. Carswell EA, Old LJ, Kassel RL, Green S, Fiore N, Williamson B (1975) An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci USA 72: 3666–3670PubMedGoogle Scholar
  35. Casey ML, Beutler B, MacDonald PC (1989) Cachectin/tumor necrosis factor-alpha action in human amnion and decidua: potential role in infection-associated preterm labor. J Clin Invest 83: 430–136PubMedGoogle Scholar
  36. Cerami A, Ikeda Y, Le Trang N, Hotez PJ, Beutler B (1985) Weight loss associated with an endotoxin-induced mediator from peritoneal macrophages: the role of cachectin (tumor necrosis factor). Immunol Lett 11: 173–177PubMedGoogle Scholar
  37. Chen AR, McKinnon KP, Koren HS (1985) Lipopolysaccharide (LPS) stimulates fresh human monocytes to lyse actinomycin D-treated WEHI-164 target cells via increased secretion of a monokine similar to tumor necrosis factor. J Immunol 135: 3978–3987PubMedGoogle Scholar
  38. Chojkier M, Fierer J (1985) D-Galactosamine hepatotoxicity is associated with endotoxin sensitivity and mediated by lymphoreticular cells in mice. Gastroenterology 88:115–121Google Scholar
  39. Clark IA (1978) Does endotoxin cause both the disease and parasite death in acute malaria and babesiosis? Lancet 2: 75–77PubMedGoogle Scholar
  40. Clark IA (1979) Resistance to Babesia spp. and Plasmodium sp. in mice pretreated with an extract of Coxiella burnetii. Infect Immun 24: 319–325PubMedGoogle Scholar
  41. Clark IA (1982a) Suggested importance of monokines in pathophysiology of endotoxin shock and malaria. Klin Wochenschr 60: 756–758PubMedGoogle Scholar
  42. Clark IA (1982b) Correlation between susceptibility to malaria and babesis parasites and the endotoxicity. Trans R Soc Trop Med Hyg 76: 4–7PubMedGoogle Scholar
  43. Clark IA, Yirelizier JL, Carswell EA, Wood PR (1981) Possible importance of macrophage-derived mediators in acute malaria. Infect Immun 32: 1058–1066PubMedGoogle Scholar
  44. Clark I A, Cowden WB, Butcher GA, Hunt NH (1987) Possible roles of tumor necrosis factor in the pathology of malaria. Am J Pathol 129: 192–199PubMedGoogle Scholar
  45. Coley WB (1893) The treatment of malignant tumors by repeated inoculations of erysipelas; with a report of ten original cases. Am J Med Sci 105: 487–511Google Scholar
  46. Coley WB (1906) Late results of the treatment of inoperable sarcoma by the mixed toxins of erysipelas and Bacillus prodigiosus. Am J Med Sci 131: 375–430Google Scholar
  47. Collart MA, Berlin D, Vassalli JD, DeKossodo S, Vassalli P (1986) Gamma interferon enhances macrophage transcription of the tumor necrosis factor/cachectin, inter-leukin 1, and urokinase genes, which are controlled by short-lived repressors. J Exp Med 164: 2113–2118PubMedGoogle Scholar
  48. Collins T, Lapierre LA, Fiers W, Strominger JL, Pober JS (1986) Recombinant human tumor necrosis factor increases mRNA levels and surface expression of HLA-A,B antigens in vascular endothelial cells and dermal fibroblasts in vitro. Proc Natl Acad Sci 83: 446–450PubMedGoogle Scholar
  49. Colotta F, Lampugnani MG, Polentarutti N, Dejana E, Mantovani A (1988) Interleukin-1 induces c-fos protooncogene expression in cultured human endothelial cells. Biochem Biophys Res Commun 152: 1104–1110PubMedGoogle Scholar
  50. Conta BS, Powell MB, Ruddle NH (1985) Activation of LyT-1 + and LyT-2+ T cell cloned lines: stimulation of proliferation, lymphokine production, and self-destruction. J Immunol 134: 2185–2190PubMedGoogle Scholar
  51. Coombes RC, Rothwell NJ, Shah P, Stock MJ (1987) Changes in thermogenesis and brown fat activity in response to tumour necrosis factor in the rat. Biosci Rep 7: 791–799PubMedGoogle Scholar
  52. Cordingley FT, Hoffbrand AV, Heslop HE, Turner M, Bianchi A, Reittie JE, Vyakarnam A, Meager A, Brenner MK (1988) Tumour necrosis factor as an autocrine tumour growth factor for chronic B-cell malignancies. Lancet 1: 969–971PubMedGoogle Scholar
  53. Creasey AA, Yamamoto R, Vitt CR (1987) A high molecular weight component of the human tumor necrosis factor receptor is associated with cytotoxicity. Proc Natl Acad Sci USA 84: 3293–3297PubMedGoogle Scholar
  54. Cuturi MC, Murphy M, Costa-Giomi MP, Weinmann R, Perussia B, Trinchieri G (1987) Independent regulation of tumor necrosis factor and lymphotoxin production by human peripheral blood lymphocytes. J Exp Med 165: 1581–1594PubMedGoogle Scholar
  55. Cybulsky MI, McComb DJ, Movat HZ (1988) Neutrophil leukocyte emigration induced by endotoxin. J Immunol 140: 3144–3149PubMedGoogle Scholar
  56. Darzynkiewicz Z, Williamson B, Carswell EA, Old LJ (1984) Cell cycle-specific effects of tumor necrosis factor. Cancer Res 44: 83–90PubMedGoogle Scholar
  57. Davis JM, Narachi MA, Alton NK, Arakawa T (1987) Structure of human tumor necrosis factor alpha derived from recombinant DNA. Biochemistry 26: 1322–1326PubMedGoogle Scholar
  58. Dayer J-M, Beutler B, Cerami A (1985) Cachectin/tumor necrosis factor (TNF) stimulates collagenase and PGE2 production by human synovial cells and dermal fibroblasts. J Exp Med 162: 2163–2168PubMedGoogle Scholar
  59. Decker T, Lohmann-Matthes M-L, Gifford GE (1987) Cell-associated tumor necrosis factor ( TNF) as a killing mechanism of activated cytotoxic macrophages. J Immunol 138: 957–962PubMedGoogle Scholar
  60. Degliantoni G, Murphy M, Kobayashi M, Francis MK, Perussia B, Trinchieri G (1985) Natural killer (NK) cell-derived hematopoietic colony-inhibiting activity and NK cytotoxic factor. Relationship with tumor necrosis factor and synergism with immune interferon. J Exp Med 162: 1512–1530PubMedGoogle Scholar
  61. Dinarello CA, Cannon JG, Wolff SM, Bernheim HA, Beutler B, Cerami A, Palla-dino MA, O’Connor JV (1986) Tumor necrosis factor (cachectin) is an endogenous pyrogen and induces production of interleukin-1. J Exp Med 163: 1433–1450PubMedGoogle Scholar
  62. Djeu JY, Blanchard DK, Halkias D, Friedman H (1986) Growth inhibition of Candida albicans by human polymorphonuclear neutrophils: activation by interferon-gamma and tumor necrosis factor. J Immunol 137: 2980–2984PubMedGoogle Scholar
  63. Eck MJ, Beutler B, Kuo G, Merryweather JP, Sprang SR (1988) Crystallization of trimeric recombinant human tumor necrosis factor (cachectin). J Biol Chem 263: 12816–12819PubMedGoogle Scholar
  64. Enerback S, Semb H, Tavernier J, Bjursell G, Olivecrona T (1988) Tissue-specific regulation of guinea pig lipoprotein lipase; effects of nutritional state and of tumor necrosis factor on mRNA levels in adipose tissue, heart and liver. Gene 64: 97–106PubMedGoogle Scholar
  65. Esparza I, Mannel D, Ruppel A, Falk W, Krammer PH (1987) Interferon-gamma (IFN-gamma) and lymphotoxin (LT) or tumor necrosis factor ( TNF) synergize to activate macrophages for tumoricidal and schistosomulicidal functions. Lymphokine Res 6: 1715Google Scholar
  66. Ferrante A, Nandoskar M, Walz A, Goh DHB, Kowanko IC (1988) Effects of tumour necrosis factor alpha and interleukin-1 alpha and beta on human neutrophil migration, respiratory burst and degranulation. Int Arch Allergy Appl Immunol 86: 82–91PubMedGoogle Scholar
  67. Fisch H, Gifford GE (1983) In vitro production of rabbit macrophage tumor cell cytotoxin. Int J Cancer 32: 105–112PubMedGoogle Scholar
  68. Fransen L, Muller R, Marmenout A, Tavernier J, van der Heyden J, Kawashima E, Chollet A, Tizard R, Van Heuverswyn H, Van Vliet A, Ruysschaert M-R, Fiers W (1985) Molecular cloning of mouse tumour necrosis factor cDNA and its eukaryotic expression. Nucleic Acids Res 13: 4417–4429PubMedGoogle Scholar
  69. Gamble JR, Harlan JM, Klebanoff SJ, Lopez AF, Vadas MA (1985) Stimulation of the adherence of neutrophils to umbilical vein endothelium by human recombinant tumor necrosis factor. Proc Natl Acad Sci USA 82: 8667–8671PubMedGoogle Scholar
  70. Garrett R, Dune BGM, Nedwin GE, Gillespie A, Bringman T, Sabatini M, Bertolini DR, Mundy GR (1987) Production of lymphotoxin, a bone-resorbing cytokine, by cultured human myeloma cells. N Engl J Med 317: 526–532PubMedGoogle Scholar
  71. Gaskill HV III (1988) Continuous infusion of tumor necrosis factor: mechanisms of toxicity in the rat. J Surg Res 44: 664–671PubMedGoogle Scholar
  72. Ghezzi P, Saccardo B, Bianchi M (1986) Recombinant tumor necrosis factor depresses cytochrome P450–dependent microsomal drug metabolism in mice. Biochem Biophys Res Commun 136: 316–321PubMedGoogle Scholar
  73. Gifford GE, Lohmann-Matthes ML (1986) Requirement for the continual presence of lipopolysaccharide for production of tumor necrosis factor by thioglycollate-induced peritoneral murine macrophages. Int J Cancer 38: 135–137PubMedGoogle Scholar
  74. Goldberg AL, Kettelhut IC, Furuno K, Fagan JM, Baracos V (1988) Activation of protein breakdown and prostaglandin E2 production in rat skeletal muscle in fever is signaled by a macrophage product distinct from interleukin 1 or other known monokines. J Clin Invest 81: 1378–1383PubMedGoogle Scholar
  75. Grau GE, Fajardo LF, Piguet P-F, Allet B, Lambert P-H, Vassalli P (1987) Tumor necrosis factor (cachectin) as an essential mediator in murine cerebral malaria. Science 237: 1210–1212PubMedGoogle Scholar
  76. Green S, Dobrjansky A, Carswell EA, Kassel RL, Old LJ, Fiore N, Schwartz MK (1976) Partial purification of a serum factor that causes necrosis of tumors. Proc Natl Acad Sci USA 73: 381–385PubMedGoogle Scholar
  77. Ha DK, Gardner ID, Lawton JW (1983) Characterization of macrophage function in Mycobacterium lepraemurium-infected mice: sensitivity of mice to endotoxin and release of mediators and lysosomal enzymes after endotoxin treatment. Parasite Immunol 5: 513–526PubMedGoogle Scholar
  78. Haidaris CG, Haynes JD, Meltzer MS, Allison AC (1983) Serum containing tumor necrosis factor is cytotoxic for the human malaria parasite Plasmodium falciparum. Infect Immun 42: 385–393PubMedGoogle Scholar
  79. Hakoshima T, Tomita K-I (1988) Crystallization and preliminary x-ray investigation reveals that tumor necrosis factor is a compact trimer furnished with 3–fold symmetry. J Mol Biol 201: 455–457PubMedGoogle Scholar
  80. Haranaka K, Satomi N, Sakurai A, Haranaka R (1984) Role of first stimulating agents in the production of tumor necrosis factor. Cancer Immunol Immunother 18: 87–90PubMedGoogle Scholar
  81. Hartwell JL, Shear MJ, Adams JR Jr (1943) Chemical treatment of tumors. VII. Nature of the hemorrhage-producing fraction from Serratia marcescens (.Bacillus prodigiosus) culture filtrate. JNCI 4: 107–122Google Scholar
  82. Helson L, Green S, Carswell E, Old LJ (1975) Effect of tumour necrosis factor on cultured human melanoma cells. Nature 258: 731–732PubMedGoogle Scholar
  83. Hoffmann MK, Green S, Old LJ, Oettgen HF (1976) Serum containing endotoxin–induced tumour necrosis factor substitutes for helper T cells. Nature 263: 416–417PubMedGoogle Scholar
  84. Hoffmann MK, Galanos C, Koenig S, Oettgen HF (1977) B-cell activation by lipopolysaccharide. Distinct pathways for induction of mitosis and antibody production. J Exp Med 146: 1640–1647PubMedGoogle Scholar
  85. Hotez PJ, Le Trang N, Fairlamb AH, Cerami A (1984) Lipoprotein lipase suppression in 3T3–L1 cells by a haematoprotozoan-induced mediator from peritoneal exudate cells. Parasite Immunol 6: 203–209PubMedGoogle Scholar
  86. Hulsmann WC, Dubelaar M-L (1988) Effects of tumor necrosis factor (TNF) on lipolytic activities of rat heart. Mol Cell Biochem 79:147–151Google Scholar
  87. Hulsmann WC, Dubelaar M-L, de Wit LEA, Persoon NLM (1988) Cardiac lipoprotein lipase: effects of lipopolysaccharide and tumor necrosis factor. Mol Cell Biochem 79: 137–145Google Scholar
  88. Imamura K, Spriggs D, Kufe D (1987) Expression of tumor necrosis factor receptors on human monocytes and internalization of receptor bound ligand. J Immunol 139: 2989–2992PubMedGoogle Scholar
  89. Israel S, Hahn T, Holtmann H, Wallach D (1986) Binding of human TNF-alpha to high-affinity cell surface receptors: effect of IFN. Immunol Lett 12: 217–224PubMedGoogle Scholar
  90. Itoh A, Iizuka K, Natori S (1984) Induction of a TNF-like factor by murine macrophage-like cell line J774.1 on treatment with Sarcophaga lectin. FEBS Lett 175: 59–62PubMedGoogle Scholar
  91. Itoh H, Wallace RB (1985) A novel human physiologically active polypeptide. European patent application no 84105149. 3Google Scholar
  92. Jacob CO, McDevitt HO (1988) Tumour necrosis factor-alpha in murine autoimmune “lupus” nephritis. Nature 331: 356–358PubMedGoogle Scholar
  93. Jeffes EWB, Averbook B, Ulich T, Yamamoto R, Chow G, Masunaka I, Granger G (1987) Human alpha lymphotoxin and tumor necrosis factor induce inflammatory responses in normal tissue. Clin Res 35: 692AGoogle Scholar
  94. Kahler H, Shear MJ, Hartwell JL (1943) Chemical treatment of tumors. VIII. Ultracentrifugal and electrophoretic analysis of the hemorrhage-producing fraction from Serratia marcescens (.Bacillus prodigiosus) culture filtrate. JNCI 4: 123–129Google Scholar
  95. Kashiwa H, Wright SC, Bonavida B (1987) Regulation of B cell maturation and differentiation. I. Suppression of pokeweed mitogen-induced B cell differentiation by tumor necrosis factor ( TNF ). J Immunol 138: 1383–1390PubMedGoogle Scholar
  96. Kawakami M, Cerami A (1981) Studies of endotoxin-induced decrease in lipoprotein lipase activity. J Exp Med 154: 631–639PubMedGoogle Scholar
  97. Kawakami M, Pekala PH, Lane MD, Cerami A (1982) Lipoprotein lipase suppression in 3T3–L1 cells by an endotoxin-induced mediator from exudate cells. Proc Natl Acad Sci USA 79: 912–916PubMedGoogle Scholar
  98. Kawakami M, Murase T, Ogawa H, Ishibashi S, Mori N, Takaku F, Shibata S (1987) Human recombinant TNF suppresses lipoprotein lipase activity and stimulates lipolysis in 3T3–L1 cells. J Biochem 101: 331–338PubMedGoogle Scholar
  99. Kettelhut IC, Goldberg AL (1988) Tumor necrosis factor can induce fever in rats without activating protein breakdown in muscle or lipolysis in adipose tissue. J Clin Invest 81: 1384–1389PubMedGoogle Scholar
  100. Kettelhut IC, Fiers W, Goldberg AL (1987) The toxic effects of tumor necrosis factor in vivo and their prevention by cyclooxygenase inhibitors. Proc Natl Acad Sci USA 84: 4273–4277PubMedGoogle Scholar
  101. Klebanoff SJ, Vadas MA, Harlan JM, Sparks LH, Gamble JR, Agosti JM, Waltersdorph AM (1986) Stimulation of neutrophils by tumor necrosis factor. J Immunol 136: 4220–4225PubMedGoogle Scholar
  102. Koj A, Kurdowska A, Magielska-Zero D, Rokita H, Sipe JD, Dayer JM, Demczuk S, Gauldie J (1987) Limited effects of recombinant human and murine interleukin 1 and tumour necrosis factor on production of acute phase proteins by cultured rat hepatocytes. Biochem Int 14: 553–560PubMedGoogle Scholar
  103. Kornbluth RS, Edgington TS (1986) Tumor necrosis factor production by human monocytes is a regulated event: induction of TNF-alpha-mediated cellular cytotoxicity by endotoxin. J Immunol 137: 2585–2591PubMedGoogle Scholar
  104. Kriegler M, Perez C, DeFay K, Albert I, Lu SD (1988) A novel form of TNF/cachectin is a cell surface cytotoxic transmembrane protein: ramifications for the complex physiology of TNF. Cell 53: 45–53PubMedGoogle Scholar
  105. Kruys VI, Wathelet M, Poupart P, Contreras R, Fiers W, Content J, Huez G (1987) The 3’ untranslated region of the human interferon-beta mRNA has an inhibitory effect on translation. Proc Natl Acad Sci USA 84: 6030–6034PubMedGoogle Scholar
  106. Kruys VI, Wathelet MG, Huez GA (1988) Identification of a translation inhibitory element (TIE) in the 3’ untranslated region of the human interferon-beta mRNA. Gene 72: 191–200PubMedGoogle Scholar
  107. Kuli FC Jr, Jacobs S, Cuatrecasas P (1985) Cellular receptor for [125]I-labeled tumor necrosis factor: specific binding, affinity labeling, and relationship to sensitivity. Proc Natl Acad Sci USA 82: 5756–5760Google Scholar
  108. Lahdevirta J, Maury CPJ, Teppo A-M, Repo H (1988) Raised circulating cachec-tin/tumor necrosis factor in patients with the acquired immunodeficiency syndrome. Am J Med 86: 289–291Google Scholar
  109. Lee MD, Zentella A, Pekala PH, Cerami A (1987) Effect of endotoxin-induced monokines on glucose metabolism in the muscle cell line L6. Proc Natl Acad Sci USA 84: 2590–2594PubMedGoogle Scholar
  110. Lehmann V, Freudenberg MA, Galanos C (1987) Lethal toxicity of lipopolysaccharide and tumor necrosis factor in normal and γ-galactosamine-treated mice. J Exp Med 165: 657–663PubMedGoogle Scholar
  111. Leung DY, Geha RS, Newburger JW, Burns JC, Fiers W, Lapierre LA, Pober JS (1986) Two monokines, interleukin 1 and tumor necrosis factor, render cultured vascular endothelial cells susceptible to lysis by antibodies circulating during Kawasaki syndrome. J Exp Med 164: 1958–1972PubMedGoogle Scholar
  112. Libby P, Ordovas JM, Auger KR, Robbins AH, Birinyi LK, Dinarello CA (1986) Endotoxin and tumor necrosis factor induce interleukin-1 gene expression in adult human vascular endothelial cells. Am J Pathol 124: 179–185PubMedGoogle Scholar
  113. Lillehei RC, Maclean LD (1958) The intestinal factor in irreversible endotoxin shock. Ann Surg 148: 513–525PubMedGoogle Scholar
  114. Mahoney JR Jr, Beutler BA, Le Trang N, Vine W, Ikeda Y, Kawakami M, Cerami A (1985) Lipopolysaccharide-treated RAW 264.7 cells produce a mediator which inhibits lipoprotein lipase in 3T3–L1 cells. J Immunol 134: 1673–1675PubMedGoogle Scholar
  115. Mannel DN, Moore RN, Mergenhagen SE (1980) Macrophages as a source of tumoricidal activity (tumor-necrotizing factor). Infect Immun 30: 523–530PubMedGoogle Scholar
  116. Mannel DN, Falk W, Northoff H (1987) Endotoxic activities of tumor necrosis factor independent of IL1 secretion by macrophages/monocytes. Lymphokine Res 6: 151–159PubMedGoogle Scholar
  117. Mathison JC, Wolfson E, Ulevitch RJ (1988) Participation of tumor necrosis factor in the mediation of gram negative bacterial lipopolysaccharide-induced injury in rabbits. J Clin Invest 81: 1925–1937PubMedGoogle Scholar
  118. Matthews N (1978) Tumour-necrosis factor from the rabbit. II. Production by monocytes. Br J Cancer 38: 310–315PubMedGoogle Scholar
  119. Matthews N (1981a) Tumour-necrosis factor from the rabbit. V. Synthesis in vitro by mononuclear phagocytes from various tissues of normal and BCG-injected rabbits. Br J Cancer 44: 418–424PubMedGoogle Scholar
  120. Matthews N (1981b) Production of an anti-tumour cytotoxin by human monocytes. Immunology 44: 135–142PubMedGoogle Scholar
  121. McCann SM, Rettori V, Milenkovic L, Jurcovicova J, Snyder G, Beutler B (1989) Role of interleukin 1 and cachectin in control of anterior pituitary hormone release. In: Perez-Polo JR (ed) Neural control of reproductive function. Liss, New York (in press)Google Scholar
  122. Michalek SM, Moore RN, McGhee JR, Rosenstreich DL, Mergenhagen SE (1980) The primary role of lymphoreticular cells in the mediation of host responses to bacterial endotoxin. J Infect Dis 141: 55–63PubMedGoogle Scholar
  123. Michie HR, Spriggs DR, Rounds J, Wilmore DW (1987) Does cachectin cause cachexia? Surg Forum 38: 38–40Google Scholar
  124. Ming WJ, Bersani L, Mantovani A (1987) Tumor necrosis factor is chemotactic for monocytes and polymorphonuclear leukocytes. J Immunol 138: 1469–1474PubMedGoogle Scholar
  125. Moldawer LL, Andersson C, Gelin J, Lundholm KG (1988) Regulation of food intake and hepatic protein synthesis by recombinant-derived cytokines. Am J Physiol 254: G450–G456PubMedGoogle Scholar
  126. Muller U, Jongeneel CV, Nedospasov SA, Lindahl KF, Steinmetz M (1987) Tumor necrosis factor and lymphotoxin genes map close to H-2D in the mouse major histocompatibility complex. Nature 325: 265–267PubMedGoogle Scholar
  127. Munker R, Gasson J, Ogawa M, Koeffler HP (1986) Recombinant human TNF induces production of granulocyte-monocyte colony-stimulating factor. Nature 323: 79–82PubMedGoogle Scholar
  128. Mustafa M (1989) Measurement of CSF cachectin (TNF-alpha) activity in experimental Haemophilus influenzae type b (Hib) meningitis (Abstr). Proc Int Conf Antimicrob Actions Chemother 28 (in press)Google Scholar
  129. Nawroth P, Bank I, Handley D, Cassimeris J, Chess L, Stern D (1986a) Tumor necrosis factor/cachectin interacts with endothelial cell receptors to induce release of interleukin 1. J Exp Med 163: 1363–1375PubMedGoogle Scholar
  130. Nawroth PP, Handley DA, Esmon CT, Stern DM (1986b) Interleukin 1 induces endothelial cell procoagulant while suppressing cell-surface anticoagulant activity. Proc Natl Acad Sci USA 83: 3460–3464PubMedGoogle Scholar
  131. Nedospasov SA, Hirt B, Shakhov AN, Dobrynin VN, Kawashima E, Accolla RS, Jongeneel CV (1986) The genes for tumor necrosis factor (TNF-alpha) and lymphotoxin (TNF-beta) are tandemly arranged on chromosome 17 of the mouse. Nucleic Acids Res 14: 7713–7725PubMedGoogle Scholar
  132. Nedwin GE, Naylor SL, Sakaguchi AY, Smith D, Jarrett-Nedwin J, Pennica D, Goed-del DV, Gray PW (1985) Human lymphotoxin and tumor necrosis factor genes: structure homology and chromosomal localization. Nucleic Acids Res 13: 6361–6373PubMedGoogle Scholar
  133. Neta R, Vogel SN, Sipe JD, Oppenheim JJ, Giclas PC, Douches SD (1987) Comparison of the in vivo effects of RIL-1 and rTNF in radioprotection, induction of CSF and of acute phase reactants. Fed Proc 46: 1200Google Scholar
  134. Oliff A, Defeo-Jones D, Boyer M, Martinez D, Kiefer D, Vuocolo G, Wolfe A, Socher SH (1987) Tumors secreting human TNF/cachectin induce cachexia in mice. Cell 50: 555–563PubMedGoogle Scholar
  135. O’Malley WE, Achinstein B, Shear MJ (1962) Action of bacterial polysaccharide on tumors. II. Damage of sarcoma 37 by serum of mice treated with Serratia marcescens polysaccharide, and induced tolerance. JNCI 29:1169–1175Google Scholar
  136. Parant MA, Parant FJ, Chedid LA (1980) Enhancement of resistance to infection by endotoxin-induced serum factor from Mycobacterium bovis BCG-infected mice. Infect Immun 28: 654–659PubMedGoogle Scholar
  137. Patton JS, Shepard HM, Wilking H, Lewis G, Aggarwal BB, Eessalu TE, Gavin LA, Grunfeld C (1986) Interferons and tumor necrosis factors have similar catabolic effects on 3T3 LI cells. Proc Natl Acad Sci USA 83: 8313–8317PubMedGoogle Scholar
  138. Patton JS, Peters PM, McCabe J, Crase D, Hansen S, Chen AB, Liggitt D (1987) Development of partial tolerance to the gastrointestinal effects of high doses of recombinant tumor necrosis factor-alpha in rodents. J Clin Invest 80: 1587–1596PubMedGoogle Scholar
  139. Paul NL, Ruddle NH (1988) Lymphotoxin. Annu Rev Immunol 6: 407–38PubMedGoogle Scholar
  140. Pekala PH, Kawakami M, Angus CW, Lane MD, Cerami A (1983) Selective inhibition of synthesis of enzymes for de novo fatty acid biosynthesis by an endotoxin-induced mediator from exudate cells. Proc Natl Acad Sci USA 80: 2743–2747PubMedGoogle Scholar
  141. Pennica D, Nedwin GE, Hayflick JS, Seeburg PH, Derynck R, Palladino MA, Kohr WJ, Aggarwal BB, Goeddel DV (1984) Human tumor necrosis factor: precursor structure, expression and homology to lymphotoxin. Nature 312: 724–729PubMedGoogle Scholar
  142. Pennica D, Hayflick JS, Bringman TS, Palladino MA, Goeddel DV (1985) Cloning and expression in Escherichia coli of the cDNA for murine tumor necrosis factor. Proc Natl Acad Sci USA 82: 6060–6064PubMedGoogle Scholar
  143. Perlmutter DH, Dinarello CA, Punsal PI, Colten HR (1986) Cachectin/tumor necrosis factor regulates hepatic acute-phase gene expression. J Clin Invest 78: 1349–1354PubMedGoogle Scholar
  144. Peters PM, Ortaldo JR, Shalaby MR, Svedersky LP, Nedwin GE, Bringman TS, Hass PE, Aggarwal BB, Herberman RB, Goeddel DV, Palladino MA Jr (1986) Natural killer-sensitive targets stimulate production of TNF-alpha but not TNF-beta (lymphotoxin) by highly purified human peripheral blood large granular lymphocytes. J Immunol 137: 2592–2598PubMedGoogle Scholar
  145. Piguet PF, Grau G, Allet B, Vassalli P (1987) Tumor necrosis factor (TNF) is an important mediator of the mortality and morbidity induced by the graft-versus-host reaction (GVHR) ( Abstr ). Immunobiology 175: 27Google Scholar
  146. Pingleton WW, Coalson JJ, Guenter CA (1975) Significance of leukocytes in endotoxic shock. Exp Mol Pathol 22: 183–194PubMedGoogle Scholar
  147. Plata-Salamän CR, Oomura Y, Kai Y (1988) Tumor necrosis factor and interleukin-lß: suppression of food intake by direct action in the central nervous system. Brain Res 448: 106–114PubMedGoogle Scholar
  148. Playfair JHL, Taverne J, Matthews N (1984) What is tumour necrosis factor really for. Immunol Today 5: 165–166Google Scholar
  149. Plela TH, Korn JH (1987) Lymphocyte-flbroblast adhesion induced by interferon gamma and tumor necrosis factor. Arthritis Rheum 30: S90Google Scholar
  150. Pober JS, Gimbrone MA Jr, Lapierre LA, Mendrick DL, Fiers W, Rothlein R, Springer TA (1986a) Overlapping patterns of activation of human endothelial cells by interleukin 1, tumor necrosis factor, and immune interferon. J Immunol 137: 1893–1896PubMedGoogle Scholar
  151. Pober JS, Bevilacqua MP, Mendrick DL, Lapierre LA, Fiers W, Gimbrone MA Jr (1986b) Two distinct monokines, interleukin 1 and tumor necrosis factor, each independently induce biosynthesis and transient expression of the same antigen on the surface of cultured human vascular endothelial cells. J Immunol 136: 1680–1687PubMedGoogle Scholar
  152. Pober JS, Lapierre LA, Stolpen AH, Brock TA, Springer TA, Fiers W, Bevilacqua MP, Mendrick DL, Gimbrone MA Jr (1987) Activation of cultured human endothelial cells by recombinant lymphotoxin: comparison with tumor necrosis factor and in-terleukin 1 species. J Immunol 138: 3319–3324PubMedGoogle Scholar
  153. Pohlman TH, Stanness KA, Beatty PG, Ochs HD, Harlan JM (1986) An endothelial cell surface factor(s) induced in vitro by lipopolysaccharide, interleukin 1, and tumor necrosis factor-alpha increases neutrophil adherence by a CDWL8–dependent mechanism. J Immunol 136: 4548–4553PubMedGoogle Scholar
  154. Robertson B, Dostal K, Daynes RA (1988) Neuropeptide regulation of inflammatory and immunologic responses: the capacity of a-melanocyte-stimulating hormone to inhibit tumor necrosis factor and IL-1–inducible biologic responses. J Immunol 140: 4300–4307PubMedGoogle Scholar
  155. Rothwell NJ (1988) Central effects of TNF-alpha on thermogenesis and fever in the rat. Bioscience Rep 8: 345–352Google Scholar
  156. Rouzer CA, Cerami A (1980) Hypertriglyceridemia associated with Trypanosoma brucei brucei infection in rabbits: role of defective triglyceride removal. Mol Biochem Parasitol 2: 31–38PubMedGoogle Scholar
  157. Rubin BY, Anderson SL, Sullivan SA, Williamson BD, Carswell EA, Old LJ (1986) Nonhematopoietic cells selected for resistance to tumor necrosis factor produce tumor necrosis factor. J Exp Med 164: 1350–1355PubMedGoogle Scholar
  158. Ruddle NH (1986) Lymphotoxin production in AIDS. Immunol Today 7: 8–9Google Scholar
  159. Ruddle NH, Waksman BH (1967) Cytotoxic effect of lymphocyte-antigen interaction in delayed hypersensitivity. Science 157: 1060–1062PubMedGoogle Scholar
  160. Ruddle NH, Waksman BH (1968a) Cytotoxicity mediated by soluble antigen and lymphocytes in delayed hypersensitivity. III. Analysis of mechanism. J Exp Med 128: 1267–1279Google Scholar
  161. Ruddle NH, Waksman BH (1968b) Cytotoxicity mediated by soluble antigen and lymphocytes in delayed hypersensitivity. I. Characterization of the phenomenon. J Exp Med 128: 1237–1254Google Scholar
  162. Ruddle NH, Waksman BH (1968c) Cytotoxicity mediated by soluble antigen and lymphocytes in delayed hypersensitivity. II. Correlation of the in vitro response with skin reactivity. J Exp Med 128: 1255–1265Google Scholar
  163. Saklatvala J (1986) Tumour necrosis factor alpha stimulates resorption and inhibits synthesis of proteoglycan in cartilage. Nature 322: 547–549PubMedGoogle Scholar
  164. Sariban E, Imamura K, Luebbers R, Kufe D (1988) Transcriptional and posttranscrip-tional regulation of tumor necrosis factor gene expression in human monocytes. J Clin Invest 81: 1506–1510PubMedGoogle Scholar
  165. Sato K, Kasono K, Fujii Y, Kawakami M, Tsushima T, Shizume K (1987) Tumor necrosis factor type alpha (cachectin) stimulates mouse osteoblast-like cells (MC3T3–E1) to produce macrophage-colony stimulating activity and prostaglandin E2. Biochem Biophys Res Commun 145: 323–329PubMedGoogle Scholar
  166. Sato N, Goto T, Haranaka K, Satomi N, Nariuchi H, Mano-Hirano Y, Sawasaki Y (1986) Actions of tumor necrosis factor on cultured vascular endothelial cells: morphologic modulation, growth inhibition, and cytotoxicity. JNCI 76: 1113–1121PubMedGoogle Scholar
  167. Satomi N, Haranaka K, Kunii O (1981) Research on the production site of tumor necrosis factor ( TNF ). Jpn J Exp Med 51: 317–322PubMedGoogle Scholar
  168. Scheurich P, Ucer U, Kronke M, Pfizenmaier K (1986) Quantification and characterization of high-affinity membrane receptors for tumor necrosis factor on human leukemic cell lines. Int J Cancer 38: 127–133PubMedGoogle Scholar
  169. Scheurich P, Thoma B, Ucer U, Pfizenmaier K (1987) Immunoregulatory activity of recombinant human tumor necrosis factor (TNF)-alpha: induction of TNF receptors on human T cells and TNF-alpha-mediated enhancement of T cell responses. J Immunol 138: 1786–1790PubMedGoogle Scholar
  170. Schleef RR, Bevilacqua MP, Sawdey M, Gimbrone MA Jr, Loskutoff DJ (1988) Cytokine activation of vascular endothelium. Effects on tissue-type plasminogen activator and type 1 plasminogen activator inhibitor. J Biol Chem 263: 5797–5803PubMedGoogle Scholar
  171. Schmid DS, Tite JP, Ruddle NH (1986) DNA fragmentation: manifestation of target cell destruction mediated by cytotoxic T-cell lines, lymphotoxin-secreting helper T-cell clones, and cell-free lymphotoxin-containing supernatant. Proc Natl Acad Sci USA 83: 1881–1885PubMedGoogle Scholar
  172. Schmid DS, Hornung R, McGrath KM, Paul N, Ruddle NH (1987) Target cell DNA fragmentation is mediated by lymphotoxin and tumor necrosis factor. Lymphokine Res 6: 195–202PubMedGoogle Scholar
  173. Schweigerer L, Malerstein B, Gospodarowicz D (1987) Tumor necrosis factor inhibits the proliferation of cultured capillary endothelial cells. Biochem Biophys Res Com-mun 143: 997–1004Google Scholar
  174. Scuderi P, Lam KS, Ryan KJ, Petersen E, Salmon SE, Sterling KE, Finley PR, Ray CG, Slymen DJ (1986) Raised serum levels of tumour necrosis factor in parasitic infections. Lancet 2: 1364–1365PubMedGoogle Scholar
  175. Semb H, Peterson J, Tavernier J, Olivecrona T (1987) Multiple effects of tumor necrosis factor on lipoprotein lipase in vivo. J Biol Chem 262: 8390–8394PubMedGoogle Scholar
  176. Semon D, Kawashima E, Jongeneel CV, Shakhov AN, Nedospasov SA (1987) Nucleotide sequence of the murine TNF locus, including the TNF-alpha (tumor necrosis factor) and TNF-beta (lymphotoxin) genes. Nucleic Acids Res 15: 9083–9084PubMedGoogle Scholar
  177. Shalaby MR, Aggarwal BB, Rinderknecht E, Svedersky LP, Finkle BS, Palladino MA Jr (1985) Activation of human polymorphonuclear neutrophil functions by interferon-gamma and tumor necrosis factors. J Immunol 135: 2069–2073PubMedGoogle Scholar
  178. Shalaby MR, Palladino MA Jr, Hirabayashi SE, Eessalu TE, Lewis GD, Shepard HM, Aggarwal BB (1987) Receptor binding and activation of polymorphonuclear neutrophils by tumor necrosis factor-alpha. J Leukocyte Biol 41: 196–204PubMedGoogle Scholar
  179. Shalaby MR, Espevik T, Rice GC, Ammann AJ, Figari IS, Ranges GE, Palladino MA Jr (1988) The involvement of human tumor necrosis factors-a and–α in the mixed lymphocyte reaction. J Immunol 141: 499–503PubMedGoogle Scholar
  180. Sharpe RJ, Margolis RJ, Amento EP, Granstein RD (1987) Induction of dermal acute inflammation by tumor necrosis factor. Clin Res 35: 716AGoogle Scholar
  181. Shaw G, Kamen R (1986) A conserved AU sequence from the 3’ untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell 46: 659–667PubMedGoogle Scholar
  182. Shear MJ (1944) Chemical treatment of tumors. IX. Reactions of mice with primary subcutaneous tumors to injection of a hemorrhage-producing bacterial polysaccharide. JNCI 4: 461–476Google Scholar
  183. Shear MJ, Andervont HB (1936) Chemical treatment of tumors. III. Separation of hemorrhage-producing fraction of B. coli filtrate. Proc Soc Exp Biol Med 34: 323–325Google Scholar
  184. Shear MJ, Turner FC, Perrault A, Shovelton J (1943a) Chemical treatment of tumors. V. Isolation of the hemorrhage-producing fraction from Serratia marcescens (Baccillusprodigiosus) culture filtrate. JNCI 4: 81–97Google Scholar
  185. Shear MJ, Perrault A, Adams JR Jr (1943b) Chemical treatment of tumors. VI. Method employed in determining the potency of hemorrhage-producing bacterial preparations. JNCI 4: 99–105Google Scholar
  186. Shirai T, Yamaguchi H, Ito H, Todd CW, Wallace RB (1985) Cloning and expression in Escherichia coli of the gene for human tumour necrosis factor. Nature 313: 803–806PubMedGoogle Scholar
  187. Silberstein DS, David JR (1986) Tumor necrosis factor enhances eosinophil toxicity to Schistosoma mansoni larvae. Proc Natl Acad Sci USA 83: 1055–1059PubMedGoogle Scholar
  188. Silberstein DS, Owen WF, Gasson JC, DiPersio JF, Golde DW, Bina JC, Soberman R, Austen KF, David JR (1986) Enhancement of human eosinophil cytotoxicity and leukotriene synthesis by biosynthetic (recombinant) granulocyte-macrophage colony-stimulating factor. J Immunol 137: 3290–3294PubMedGoogle Scholar
  189. Silberstein DS, Desscin AJ, Elsas PP, Fontaine B, David JR (1987) Characterization of a factor from the U937 cell line that enhances the toxicity of human eosinophils to Schistosoma mansoni larvae. J Immunol 138: 3042–3050PubMedGoogle Scholar
  190. Sipe JD, Vogel SN, Douches S, Neta R (1987) Tumor necrosis factor/cachectin is a less potent inducer of serum amyloid A synthesis than interleukin 1. Lymphokine Res 6: 93–101PubMedGoogle Scholar
  191. Smith RA, Baglioni C (1987) The active form of tumor necrosis factor is a trimer. J Biol Chem 262: 6951–6954PubMedGoogle Scholar
  192. Smith RA, Kirstein M, Fiers W, Baglioni C (1986) Species specificity of human and murine tumor necrosis factor. J Biol Chem 261: 14871–14874PubMedGoogle Scholar
  193. Socher SH, Martinez D, Craig JB, Kuhn JG, Oliff A (1988) Tumor necrosis factor no detectable in patients with clinical cancer cachexia. JNCI 80: 595–598PubMedGoogle Scholar
  194. Spies T, Morton CC, Nedospasov SA, Fiers W, Pious D, Strominger JL (1986) Genes for the tumor necrosis factors alpha and beta are linked to the human major histocompatibility complex. Proc Natl Acad Sci USA 83: 8699–8702PubMedGoogle Scholar
  195. Stashenko P, Dewhirst FE, Peros WJ, Kent RL, Ago JM (1987) Synergistic interactions between interleukin 1, tumor necrosis factor, and lymphotoxin in bone resorption. J Immunol 138: 1464–1468PubMedGoogle Scholar
  196. Stern DM, Nawroth PP (1986) Modulation of endothelial hemostatic properties by tumor necrosis factor. J Exp Med 163: 740–745PubMedGoogle Scholar
  197. Stolpen AH, Guinan EC, Fiers W, Pober JS (1986) Recombinant tumor necrosis factor and immune interferon act singly and in combination to reorganize human vascular endothelial cell monolayers. Am J Pathol 123: 16–24PubMedGoogle Scholar
  198. Sugarman BJ, Aggarwal BB, Hass PE, Figari IS, Paladino MA Jr, Shepard HM (1985) Recombinant human tumor necrosis factor-alpha: effects on proliferation of normal and transformed cells in vitro. Science 230: 943–945PubMedGoogle Scholar
  199. Sun X-M, Hsueh W (1988) Bowel necrosis induced by tumor necrosis factor in rats is mediated by platelet-activating factor. J Clin Invest 81: 1328–1331PubMedGoogle Scholar
  200. Takeda K, Iwamoto S, Sugimoto H, Takuma T, Kawatani N, Noda M, Masaki A, Morise H, Arimura H, Konno K (1986) Identity of differentiation inducing factor and tumour necrosis factor. Nature 323: 338–340PubMedGoogle Scholar
  201. Tashjian AH, Voelkel EF, Lazzaro M, Singer FR, Roberts AB, Derynck R, Winkler ME, Levine L (1985) Alpha and beta human transforming growth factors stimulate prostaglandin production and bone resorption in cultured mouse calvaria. Proc Natl Acad Sci USA 82: 4535–538PubMedGoogle Scholar
  202. Taverne J, Dockrell HM, Playfair JH (1981) Endotoxin-induced serum factor kills malarial parasites in vitro. Infect Immun 33: 83–89PubMedGoogle Scholar
  203. Taverne J, Depledge P, Playfair JH (1982) Differential sensitivity in vivo of lethal and nonlethal malarial parasites to endotoxin-induced serum factor. Infect Immun 37: 927–934PubMedGoogle Scholar
  204. Taverne J, Matthews N, Depledge P, Playfair JH (1984) Malarial parasites and tumour cells are killed by the same component of tumour necrosis serum. Clin Exp Immunol 57: 293–300PubMedGoogle Scholar
  205. Torti FM, Dieckmann B, Beutler B, Cerami A, Ringold GM (1985) A macrophage factor inhibits adipocyte gene expression: an in vitro model of cachexia. Science 229: 867–869PubMedGoogle Scholar
  206. Tracey KJ, Lowry S, Beutler B, Cerami A, Albert J, Shires GT (1986a) Cachec-tin/tumor necrosis factor mediates changes in skeletal muscle transmembrane potential. J Exp Med 164: 1368–1373PubMedGoogle Scholar
  207. Tracey KJ, Beutler B, Lowry SF, Merryweather J, Wolpe S, Milsark IW, Hariri RJ, Fahey TJ III, Zentella A, Albert JD, Shires GT, Cerami A (1986b) Shock and tissue injury induced by recombinant human cachectin. Science 234: 470–474PubMedGoogle Scholar
  208. Tracey KJ, Lowry SF, Fahey TJ III, Albert JD, Fong Y, Hesse D, Beutler B, Manogue KR, Calvano S, Wei H, Cerami A, Shires GT (1987a) Cachectin/tumor necrosis factor induces lethal shock and stress hormone responses in the dog. Surg Gynecol Obstet 164: 415–422PubMedGoogle Scholar
  209. Tracey KJ, Fong Y, Hesse DG, Manogue KR, Lee AT, Kuo GC, Lowry SF, Cerami A (1987b) Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia. Nature 330: 662–666PubMedGoogle Scholar
  210. Tracey KJ, Wei H, Manogue KR, Fong Y, Hesse DG, Nguyen HT, Kuo GC, Beutler B, Cotran RS, Cerami A, Lowry SF (1988) Cachectin/tumor necrosis factor induces cachexia, anemia, and inflammation. J Exp Med 167: 1211–1227PubMedGoogle Scholar
  211. Troppmair J, Aubock J, Niederwieser D, Schonitzer D, Huber C (1988) Interferons (IFN’s) and tumor necrosis factors (IFN’s) in T cell-mediated immune responses against alloantigens. I. Influence on the activation of resting and antigen-primed T cells. Immunobiology 176: 236–254PubMedGoogle Scholar
  212. Tsujimoto M, Yokota S, Vilcek J, Weissmann G (1986) Tumor necrosis factor provokes superoxide anion generation from neutrophils. Biochem Biophys Res Commun 137: 1094–1100PubMedGoogle Scholar
  213. Umeda T, Hara T, Niijima T (1983) Cytotoxic effect of tumor necrosis factor on human lymphocytes and specific binding of the factor to the target cells. Cell Mol Biol 29: 349–352PubMedGoogle Scholar
  214. Vilcek J, Palombella VJ, Henriksen-Destefano D, Swenson C, Feinman R, Hirai M, Tsujimoto M (1986) Fibroblast growth enhancing activity of tumor necrosis factor and its relationship to other polypeptide growth factors. J Exp Med 163: 632–643PubMedGoogle Scholar
  215. Vlassara H, Brownlee M, Manogue KR, Dinarello CA, Pasagian A (1988) Cachec-tin/TNF and IL-1 induced by glucose-modified proteins: role in normal tissue remodeling. Science 240: 1546–1548PubMedGoogle Scholar
  216. Vogel SN, Moore RN, Sipe JD, Rosenstreich DL (1980) BCG-induced enhancement of endotoxin sensitivity in C3H/He J mice. I. In vivo studies. J Immunol 124: 2004–2009Google Scholar
  217. Waage A, Halstensen A, Espevik T (1987) Association between tumour necrosis factor in serum and fatal outcome in patients with meningococcal disease. Lancet 1(8529):355–357Google Scholar
  218. Wallach D, Holtmann H, Engelmann H, Nophar Y (1988) Sensitization and desensitization to lethal effects of tumor necrosis factor and 11–1. J Immunol 140: 2994–2999PubMedGoogle Scholar
  219. Wang AM, Creasey AA, Ladner MB, Lin LS, Strickler J, van Arsdell JN, Yamamoto R, Mark DF (1985) Molecular cloning of the complementary DNA for human tumor necrosis factor. Science 228: 149–154PubMedGoogle Scholar
  220. Warren MK, Ralph P (1986) Macrophage growth factor CSF-1 stimulates human monocyte production of interferon, tumor necrosis factor, and colony stimulating activity. J Immunol 137: 2281–2285PubMedGoogle Scholar
  221. Watanabe N, Sone H, Neda H, Niitsu Y, Urushizaki I (1984) Mechanisms of production of tumor necrosis factor (TNF): reconstitution experiment with nude mice. Gan To Kagaku Ryoho 11. 1284–1289PubMedGoogle Scholar
  222. Wei H, Tracey K, Manogue K, Nguyen H, Fong Y, Hesse D, Beutler B, Solomon R, Cerami A, Lowry S (1987) Cachetin mediates suppressed food intake and anemia during chronic administration, Fed Proc 46:1338Google Scholar
  223. Wood PR, Clark IA (1984) Macrophages from Babesia and malaria infected mice are primed for monokine release. Parasite Immunol 6: 309–317PubMedGoogle Scholar
  224. Wozencraft AO, Dockrell HM, Taverne J, Targett GAT, Playfair JHL (1984) Killing of human malaria parasites by macrophage secretory products. Infect Immun 43: 664–669PubMedGoogle Scholar
  225. Yoshie O, Tada K, Ishida N (1986) Binding and crosslinking of 1251–labeled recombinant human tumor necrosis factor to cell surface receptors. J Biochem 100: 531–541PubMedGoogle Scholar
  226. Zacharchuk CM, Drysdale B-E, Mayer MM, Shin HS (1983) Macrophage-mediated cytotoxicity: role of a soluble macrophage cytotoxic factor similar to lymphotoxin and tumor necrosis factor. Proc Natl Acad Sci USA 80: 6341–6345PubMedGoogle Scholar
  227. Zechner R, Newman TC, Sherry B, Cerami A, Breslow JL (1988) Recombinant human cachectin/tumor necrosis factor but not interleukin-la downregulates lipoprotein lipase gene expression at the transcriptional level in mouse 3T3–L1 adipocytes. Mol Cell Biol 8: 2394–2401PubMedGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 1990

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  • B. Beutler

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