Skip to main content
SpringerLink
Log in

Interleukin-6 and its receptor during homeostasis, inflammation, and tumor growth

  • Übersicht
  • Published:
Klinische Wochenschrift Aims and scope Submit manuscript

Summary

This review focuses on describing the specific role of interleukin-6 within the network of inflammatory mediators in man. Sites of interleukin-6 synthesis, regulation of its expression, and the biological functions of this molecule are here outlined. The potential role of interleukin-6 as a diagnostic monitor is discussed. Particular attention is paid to experimental evidence that interleukin-6 and its receptor may be involved in the pathogenesis of autocrine tumor growth. A recently proposed therapeutical use of cytotoxic interleukin-6 fusion proteins in order to selectively destroy certain interleukin-6 receptor bearing tumor cells is discussed in the light of the finding, that not only hepatocytes, but also normal peripheral blood monocytes express the interleukin-6 receptor.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

ACTH:

Adenocorticotropic hormone

BCDF:

B-cell differentiation factor

BSF-2:

B-cell stimulatory factor 2

bp:

base pairs

CAT:

chloramphenicol acetyltransferase

cDNA:

complementary deoxyribonucleic acid

cAMP:

cyclic adenosinmonophosphate

CHX:

cycloheximid

CRP:

C-reactive protein

DNA:

deoxyribonucleic acid

EBV:

Epstein Barr Virus

FACS:

fluorescence activated cell sorter

GMCSF:

granulocyte-monocyte colony stimulating factor

HSF:

hepatocyte stimulating factor

HGF:

hybridoma growth factor

IFNβ 2:

interferon beta 2

IL-1:

interleukin-1

IL-3:

interleukin-3

IL-6:

interleukin-6

IL6R:

interleukin-6 receptor

kDa:

kilo-dalton

LPS:

lipopolysaccharide/endotoxin

M-CSF:

macrophage colony stimulating factor

mRNA:

messenger ribonucleic acid

PDGF:

platelet-derived growth factor

RNA:

ribonucleic acid

SAC:

Staphylococchus aureus Cowan I

TNF:

tumor necrosis factor/cachectin

References

  1. Aarden L, Lansdorp P, De Groot E (1985) A growth factor for B cell hybrodimas produced by human monocytes. Lymphokines 10:175–185

    Google Scholar 

  2. Aarden LA, De Groot ER, Schaap OL, Lansdorp PM (1987) Production of hybridoma growth factor by human monocytes. Eur J Immunol 17:1411–1416

    Google Scholar 

  3. Andus T, Geiger T, Hirano T, Northoff H, Ganter U, Bauer J, Kishimoto T, Heinrich PC (1987) Recombinant human B cell stimulatory factor 2 (BSF-2/IFN-β2) regulatesβ-fibrinogen and albumin mRNA levels in Fao-9 cells. FEBS Lett 221:18–22

    Google Scholar 

  4. Andus T, Geiger T, Hirano T, Kishimoto T, Heinrich PC (1988) Action of recombinant interleukin6, interleukin 1β and tumor necrose factor α on the mRNA induction of acute-phase proteins. Eur J Immunol 18:739–746

    Google Scholar 

  5. Andus T, Geiger T, Hirano T, Kishimoto T, Tran-Thi TA, Decker K, Heinrich PC (1988) Regulation of synthesis and secretion of major rat acute-phase proteins by recombinant human interleukin-6 in hepatocyte primary cultures. Eur J Biochem 173:287–239

    Google Scholar 

  6. Arcone R, Gualandi G, Ciliberto G (1988) Identification of sequences responsible for acute phase induction of human C-reactive protein. Nucl Acid Res 16:3195–3207

    Google Scholar 

  7. Asaoku H, Kawano M, Iwato K, Tanabe O, Tanaka H, Hirano T, Kishimoto T, Kuramoto A (1988) Decrease in BSF-2/IL-6 response in advanced cases of multiple myeloma. Blood 72:429–432

    Google Scholar 

  8. Bauer J, Birmelin M, Northoff GH, Northemann W, Tran-Thi TA, Ueberberg H, Heinrich PC (1984) Induction of rat alpha 2 macroglobulin in vivo and in hepatocyte primary cultures: synergistic action of glucocorticoids and a Kupffer cell derived factor. FEBS Lett 177:89–94

    Google Scholar 

  9. Bauer J, Tran-Thi TA, Northoff H, Hirsch F, Schlayer HJ, Gerok W, Heinrich PC (1986) The acute phase induction of alpha 2 macroglobulin in rat hepatocyte primary cultures: action of a hepatocyte-stimulating factor, trijodothyronine and dexamethasone. Eur J Cell Biol 40:86–93

    Google Scholar 

  10. Bauer J, Ganter U, Geiger T, Jacobshagen U, Hirano T, Matsuda T, Kishimoto T, Andus T, Acs G, Gerok W, Ciliberto G (1988) Regulation of interleukin-6 expression in cultured human blood monocytes and monocyte-derived macrophages. Blood 72:1134–1140

    Google Scholar 

  11. Bauer J, Lengyel G, Bauer TM, Acs G, Gerok W (1989) Regulation of interleukin-6 receptor expression in human monocytes and hepatocytes. FEBS Lett 249:27–30

    Google Scholar 

  12. Bauman H, Jahreis GP, Sauder DN, and Koj A (1984) Human keratinocytes and monocytes release factors which regulate the synthesis of major acute phase plasma proteins in hepatic cells from man, rat, and mouse. J Biol Chem 259:7331–7342

    Google Scholar 

  13. Baumann H, Onorato V, Gauldie J, and Jahreis GP (1987) Distinct sets of acute phase plasma proteins are stimulated by separate human hepatocyte-stimulating factors and monokines in rat hepatoma cells. J Biol Chem 262:9756–9768

    Google Scholar 

  14. Baumann H, Müller-Eberhard U (1987) Synthesis of hemopexin and cysteine proteinase inhibitor is coordinately regulated by HSF-II and interferonβ2 in rat hepatoma cells. Biochem Biophys Res Commun 146:1218–1226

    Google Scholar 

  15. Billiau A (1986) BSF-2 is not just a differentiation factor. Nature 324:415

    Google Scholar 

  16. Bot FJ, van Eijk L, Broeders L, Aarden LA, Löwenberg B (1989) Interleukin-6 synergizes with M-CSF in the formation of macrophage colonies from purified human marrow progenitor cells. Blood 73:425–437

    Google Scholar 

  17. Brakenhoff JPJ, De Groot ER, Evers RF, Pannekoek H, Aarden L (1987) Molecular cloning and expression of hybridoma growth factor in Escherichia coli. J Immunol 139:4116–4121

    Google Scholar 

  18. Caracciolo D, Clark SC, Rovera G (1989) Human interleukin-6 supports granulocytic differentiation of hematopoictic progenitor cells and acts synergistically with GM-CSF. Blood 73:666–670

    Google Scholar 

  19. Castell JV, Gomez-Lechon MJ, David M, Hirano T, Kishimoto T, Heinrich PC (1988) Recombinant human interleukin-6 (IL-6/BSF-2/HSF) regulates the synthesis of acute phase proteins in human hepatocytes. FEBS Lett 232:347–350

    Google Scholar 

  20. Castell JV, Geiger T, Gross V, Andus T, Walter E, Hirano T, Kishimoto T, Heinrich PC (1988) Plasma Clearance, organ distribution and target cells of interleukin-6/hepatocyte-stimulating factor in the rat. Eur J Biochem 177:357–361

    Google Scholar 

  21. Castell JV, Gomez-Lechon MJ, David M, Andus T, Geiger T, Trullenque R, Fabra R, Heinrich PC (1989) Interleukin-6 is the major regulator of the acute phase protein synthesis in adult human hepatocytes. FEBS Lett 242:237–239

    Google Scholar 

  22. Castelman B, Iverson L, Menendez VP (1986) Localised mediastinal lymphnode hyperplasia resembling thymoma. Cancer 9:822–828

    Google Scholar 

  23. Chen L, Mory Y, Zilberstein A, Revel M (1988) Growth inhibition of human breast carcinoma and leukemia/lymphoma cell lines by recombinant interferonβ2. Proc Natl Acad Sci USA 85:8037–8041

    Google Scholar 

  24. Chen L, Novick D, Rubinstein M, Revel M (1988) Recombinant interferon-β2 (interleukin-6) induces myeloid differentiation. FEBS Lett 239:299–304

    Google Scholar 

  25. Content J, De Wit L, Pierard D, Derynck R, De Clercq E, Fiers W (1982) Secretory proteins induced in human fibroblasts under conditions used for the production of interferonβ. Proc Natl Acad Sci USA 79:2768–2772

    Google Scholar 

  26. Content J, De Wit L, Poupart P, Opdenakker G, Van Damme J, Billiau A (1985) Induction of a 26-kDA-protein mRNA in human cells treated with an interleukin-1-related, leukocyte-derived factor. Eur J Biochem 152:253–257

    Google Scholar 

  27. Defilippi P, Poupart P, Tavernier J, Fiers W, Content J (1987) Induction and regulation of mRNA encoding 26-kDA protein in human cell lines treated with recombinant human tumor necrosis factor. Proc Natl Acad Sci USA 84:4557–4561

    Google Scholar 

  28. Dinarello CA (1984) Induction of the acute phase reactants by interleukin-1. Adv in Inflamm Res 8:223–225

    Google Scholar 

  29. Dinarello CA (1984) Interleukin-1 and the pathogenesis of the acute-phase response. N Engl J Med 311:1413–1418

    Google Scholar 

  30. Elias JA, Trinchieri G, Beck JM, Simon PL, Sehgal PB, May LT, Kern JA (1989) A synergistic interaction of IL-6 and IL-1 mediates the thymocyte-stimulating activity produced by recombinant IL-1-stimulated fibroblasts. J Immunol 142:509–514

    Google Scholar 

  31. Fey GH, Fuller GM (1987) Regulation of acute phase gene expression by inflammatory mediators. Mol Biol. Med 4:323–339

    Google Scholar 

  32. Fong Y, Moldawer LL, Marano M, Wei H, Tatter SB, Clarick RH, Santhanam U, Sherris D, May LT, Sehgal PB, Lowry SF (1989) Endotoxemia elicits increased circulatingβ2-IFN/IL-6 in man. J Immunol 142:2321–2324

    Google Scholar 

  33. Freeman GI, Freedman AS, Rabinowe SN, Segil IM, Horowitz I, Rosen K, Whitman IF, Nadler LM (1989) Interleukin 6 gene expression in normal and neoplastic B cells. J Clin Invest 83:1512–1518

    Google Scholar 

  34. Frei K, Malipiero UV, Leist TP, Zinkernagel RM, Schwab ME, Fontana A (1989) On the cellular source and function of interleukin 6 produced in the central nervous system in viral disease. Eur J Immunol 19:689–694

    Google Scholar 

  35. Fuller GM, Bunzel RJ, Woloski BM, Nham SU (1987) Isolation of hepatocyte stimulating factor from human monocytes. Biochem Biophys Res Commun 144:1003–1009

    Google Scholar 

  36. Ganter U, Arcone R, Toniatti C, Ciliberto G (1989) Dual control of CRP gene expression by interleukin 1 and interleukin 6. (Submitted)

  37. Garman RD, Jacobs KA, Clark SC, Raulet DH (1987) B-cell-stimulatory factor 2 (β2 interferon) functions as a second signal for interleukin 2 production by mature T cells. Proc Natl Acad Sci USA 84:7629–7633

    Google Scholar 

  38. Gauldie J, Richards C, Harnish D, Lansdorp P, Baumann H (1987) Interferon β2/B-cell stimulatory factor type 2 shares identity with monocyte-derived hepatocyte-stimulating factor and regulates the major acute phase protein response in liver cells. Proc Natl Acad Sci USA 84:7251–7255

    Google Scholar 

  39. Geiger T, Andus T, Bauer J, Northoff H, Ganter U, Hirano T, Kishimoto T, Heinrich PC (1988) Cell-free-synthesized interleukin-6 (BSF-2/IFNβ2) exhibits hepatocytestimulating factor activity. Eur J Biochem 175:181–186

    Google Scholar 

  40. Geiger T, Andus T, Klapproth J, Hirano T, Kishimoto T, Heinrich PC (1988) Induction of rat acute-phase proteins by interleukin 6 in vivo. Eur J Immunol 18:717–721

    Google Scholar 

  41. Gross V, Andus T, Castell J, Vom Berg D, Heinrich PC, Gerok W (1989) O- and N-glycosilation lead to different molecular mass forms of human monocyte interleukin-6. FEBS Lett 247:323–326

    Google Scholar 

  42. Haegeman G, Content J, Volckaert G, Derynck R, Tavernier J, Fiers W (1986) Structural analysis of the sequence coding for an inducible 26-kDa protein in human fibroblasts. Eur J Biochem 159:625–632

    Google Scholar 

  43. Helfgott DC, May LT, Sthoeger Z, Tamm I, Sehgal PB (1987) Bacterial lipopolysaccharide (endotoxin) enhances expression and secretion of β2 interferon by human fibroblasts. J Exp Med 166:1300–1308

    Google Scholar 

  44. Helfgott DC, Tatter SB, Santhanam U, Clarick RH, Bhardwaj N, May LT, Sehgal PB (1989) Multiple forms of IFN β2/IL-6 in serum and body fluids during acute bacterial infection. J Immunol 142:948–953

    Google Scholar 

  45. Hirano T, Taga T, Nakano N, Yasukawa K, Kashiwamura S, Shimizu K, Nakajima K, Pyun KH, Kishimoto T (1985) Purification to homogeneity and characterization of human B-cell differentiation factor (BCDF or BSFp-2). Proc Natl Acad Sci USA 82:5490–5494

    Google Scholar 

  46. Hirano T, Yasukawa K, Harada H, Taga T, Watanabe Y, Matsuda T, Kashiwamura S, Nakajima K, Koyama K, Iwamatsu A, Tsunasawa S, Sakiyama F, Matsui H, Takahara Y, Taniguchi T, Kishimoto T (1986) Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin. Nature 324:73–76

    Google Scholar 

  47. Hirano T, Matsuda T, Turner M, Miyasaka N, Buchan G, Tang B, Sato K, Shimizu M, Maini R, Feldman M, Kishimoto T (1988) Excessive production of interleukin 6/B cell stimulatory factor-2 in rheumatoid arthritis. Eur J Immunol 18:1797–1801

    Google Scholar 

  48. Hirata Y, Taga T, Hibi M, Nakano N, Hirano T, Kishimoto T (1989) Characterization of IL-6 receptor expression by monoclonal and polyclonal antibodies. (Submitted)

  49. Hoang T, Haman A, Goncalves O, Wong GG, Clark SC (1988) Interleukin-6 enhances growth factor-dependent proliferation of the blast cells of acute myeloblastic leukemia. Blood 72:823–826

    Google Scholar 

  50. Horii Y, Maraguchi A, Suematsu S, Matsuda T, Yoshizaki K, Hirano T, Kishimoto T (1988) Regulation of BSF-2/IL-6 production by human mononuclear cells. J Immunol 141:1529–1535

    Google Scholar 

  51. Houssiau FA, Coulie PG, Olive D, Van Snick J (1988) Synergistic activation of human T cells by interleukin 1 and interleukin 6. Eur J Immunol 18:653–656

    Google Scholar 

  52. Houssiau FA, Bukasa K, Sindic CJM, Van Damme J, Van Snick J (1988) Elevated levels of the 26K human hybridoma growth factor (interleukin 6) in cerebrospinal fluid of patients with acute infection of the central nervous system. Clin Exp Immunol 71:320–323

    Google Scholar 

  53. Ikebuchi K, Wong GG, Clark SC, Ihle JN, Hirai Y, Ogawa M (1987) Interleukin 6 enhancement of interleukin-3 dependent proliferation of multipotential hemopoietic progenitors. Proc Natl Acad Sci 84:9035–9039

    Google Scholar 

  54. Jablons DM, Mule JJ, McIntosh JK, Sehgal PB, May LT, Huang CM, Rosenberg SA, Lotze MT (1989) IL-6/IFN β2 as a circulating hormone. J Immunol 142:1542–1547

    Google Scholar 

  55. Jambou RC, Snouwaert JN, Bishop GA, Stebbins JR, Frellinger JA, Fowlkes DM (1988) High-level expression of a bioengineered, cysteine-free hepatocyte-stimulating factor (interleukin 6)-like protein. Proc Natl Acad Sci USA 85:9426–9430

    Google Scholar 

  56. Jirik FR, Podor TJ, Hirano T, Kishimoto T, Loskutoff DJ, Carson DA, Lotz M (1989) Bacterial lipopolysaccharide and inflammatory mediators augment IL-6 secretion by human endothelial cells. J Immunol 142:144–147

    Google Scholar 

  57. Kawano M, Hirano T, Matsuda T, Taga T, Horii Y, Iwato K, Asaoku H, Tang B, Tanabe O, Tanaka H, Kuramoto A, Kishimoto T (1988) Autocrine generation and requirement of BSF-2/IL-6 for human multiple myeloma. Nature 332:83–85

    Google Scholar 

  58. Keller AR, Hochholzer L, Castleman B (1972) Hyaline-vascular and plasma-cell types of giant lymph node hyperplasia of the mediastinum and other locations. Cancer 29:670–683

    Google Scholar 

  59. Kishimoto T: B cell stimulatory factors (BSFs) (1987) Moleculare structure, biological function, and regulation of expression. J Clin Immunol 7:343–355

    Google Scholar 

  60. Kishimoto T, Hirano T (1988) Molecular regulation of B lymphocyte response. Ann Rev Immunol 6:485–512

    Google Scholar 

  61. Kohase M, Henriksen-DeStefano D, May LT, Vilcek J, Sehgal PB (1986) Induction of β2-interferon by tumor necrosis factor: a homeostatic mechanism in the control of cell proliferation. Cell 45:659–666

    Google Scholar 

  62. Kohase M, May LT, Tamm I, Vilcek J, Sehgal PB (1987) A cytokine network in human diploid fibroblasts: interactions of β-interferons, tumor necrosis factor, platelet-derived growth factor, and interleukin-1. Mol Cell Biol 7:273–280

    Google Scholar 

  63. Koj A, Gauldie J, Regoeczi E, Sauder DN, Sweeney GD (1984) The acute phase response of cultured rat hepatocytes. Biochem J 224:505–514

    Google Scholar 

  64. Leary AG, Ikebuchi K, Hirai Y, Wong GG, Yang YC, Clark SC, Ogawa M (1988) Synergism between interleukin-6 and interleukin-3 in supporting proliferation of human hematopoietic stem cells: comparison with interleukin-1alpha. Blood 71:1759–1763

    Google Scholar 

  65. Li SP, Liu TY, Goldman ND (1988) Identification of the cis-acting elements responsible for C-reactive protein gene expression. FASEB J 2:A1246 (Abstract)

  66. Majello B, Arcone R, Toniatti C, Ciliberto G (1989) Identification of constitutional and IL-6-inducible hepatocyte nuclear factors that interact with the CRP promotor. (Submitted)

  67. Matsuda T, Hirano T, Kishimoto T (1988) Establishment of interleukin 6-dependent cell line and preparation of anti-IL 6 monoclonal antibody. Eur J Immunol 18:951–956

    Google Scholar 

  68. May LT, Helfgott DC, Sehgal PB (1986) Anti-β-interferon antibodies inhibit the increased expression of HLA-B7 mRNA in tumor necrosis factor-treated human fibroblasts: structural studies of the β2 interferon involved. Proc Natl Acad Sci USA 83:8957–8961

    Google Scholar 

  69. May LT, Ghrayeb J, Santhanam U, Tatter SB, Sthoeger Z, Helfgott DC, Chiorazzi N, Grieninger G, Sehgal PB (1988) Synthesis and secretion of multiple forms of β2-interferon/B-cell differentiation factor 2/hepatocyte-stimulating factor by human finroblasts and monocytes. J Biol Chem 263:7760–7766

    Google Scholar 

  70. May LT, Santhanam U, Tatter SB, Bhardwaj N, Ghrayeb J, Sehgal PB (1988) Phosphorylation of secreted forms of human β2-interferon/hepatocyte stimulating factor/interleukin-6. Biochem Biophys Res Commun 152:1144–1150

    Google Scholar 

  71. May LT, Torcia G, Cozzolino F, Ray A, Tatter SB, Santhanam U, Sehgal PB, Stern D (1989) Interleukin-6 gene expression in human endothelial cells: RNA start sites, multiple IL-6 proteins and inhibition of proliferation. Biochem Biophys Res Commun 159:991–998

    Google Scholar 

  72. Mock BA, Nordan RP, Justice MJ, Kozak C, Jenkins NA, Copeland NG, Clark SC, Wong GG, Rudikoff S (1989) The murine IL-6 gene maps of the proximal region of chromosome 5. J Immunol 142:1372–1376

    Google Scholar 

  73. Morrone G, Ciliberto G, Oliviero S, Arcone R, Dente L, Content J, Cortese R (1988) Recombinant interleukin 6 regulates the transcriptional activation of a set of human acute phase genes. J Biol Chem 263:12554–12558

    Google Scholar 

  74. Moshage HJ, Roelofs HMJ, Van Pelt JF, Hazenberg BPC, Van Leeuwen MA, Limburg PC, Aarden LA, Yap SH (1988) The effect of interleukin-1, interleukin-6 and its interrelationship on the synthesis of serum amyloid A and C-reactive protein in primary cultures of adult human hepatocytes. Biochem Biophys Res Commun 155:112–117

    Google Scholar 

  75. Muraguchi A, Hirano T, Tang B, Matsuda T, Horii Y, Nakajima K, Kishimoto T (1988) The essential role of B cell stimulatory factor 2 (BSF-2/IL-6) for the terminal differentiation of B cells. J Exp Med 167:332–344

    Google Scholar 

  76. Nijsten MWN, De Groot ER, Ten Duis HJ, Klasen HJ, Hack CE, Aarden LA (1987) Serum levels of interleukin-6 and acute phase responses. Lancet Oct 17:921

    Google Scholar 

  77. Norioka K, Hara M, Harigai M, Kitani A, Hirose T, Suzuki K, Kawakami M, Tabata H, Kawagoe M, Nakamura H (1988) Production of B cell stimulatory factor-2/interleukin-6 activity by human endothelial cells. Biochem Biophys Res Commun 153:1045–1050

    Google Scholar 

  78. Northoff H, Andus T, Tran-Thi TA, Bauer J, Decker K, Kubanek B, Heinrich PC (1987) The inflammation mediators interleukin1 and hepatocyte stimulating factor are differently regulated in human monocytes. Eur J Immunol 17:707–711

    Google Scholar 

  79. O'Garra A (1989) Peptide regulatory factors: interleukins and the immune system. Lancet 8644:943–947

    Google Scholar 

  80. Oliviero S, Cortese R (1989) The human haptoglobin gene promotor: interleukin-6-responsive elements interact with a cDNA-binding protein induced by interleukin-6. EMBO J 8:1145–1151

    Google Scholar 

  81. Poupart P, De Wit L, Content J (1984) Induction and regulation of the 26-kDa protein in the absence of synthesis of β-interferon mRNA in human cells. Eur J Biochem 143:15–21

    Google Scholar 

  82. Poupart P, Vandenabeele P, Cayphas S, Van Snick J, Haegeman G, Kruys V, Fiers W, Content J (1987) B cell growth modulating and differentiating activity of recombinant human 26-kd protein (BSF-2, HulFN-β2, HPGF). EMBO J 6:1219–1224

    Google Scholar 

  83. Ramadori G, Rieder H, Meuer S, Meyer zum Büschenfelde KH (1986) Interleukin-1: ein neues Hormon. Dtsch med Wochenschr 111:1031–1038

    Google Scholar 

  84. Ramadori G, Van Damme J, Rieder H, Meyer zum Büschenfelde KH (1988) Interleukin-6, the third mediator of acute-phase reaction, modulates hepatic protein synthesis in human and mouse. Comparison with interleukin 1 β and tumor necrosis factor-a. Eur J Immunol 18:1259–1264

    Google Scholar 

  85. Ray A, Tatter SB, May LT, Sehgal PB (1988) Activation of the human β2 interferon/hepatocyte-stimulating factor/interleukin-6 promotor by cytokines, viruses, and second messenger agonists. Proc Natl Acad Sci 85:6701–6705

    Google Scholar 

  86. Regulation of the acute phase and immune responses: a new cytokine. Conference sponsored by The New York Academy of Sciences and by the National Foundation for Cancer Research. December 12–14, 1988

  87. Ritchie DG, Fuller GM (1982) Regulation of hepatic fibrinogen synthesis by a monocyte-derived hepatocytestimulating factor (HSF). J Cell Biol 95:383a

    Google Scholar 

  88. Santhanam U, Ghrayeb J, Sehgal PB, May LT (1989) Post-translational and postsecretory modifications of human IFN β2/IL-6. Mol Cell Biol: in press

  89. Satoh T, Nakamura S, Taga T, Matsuda T, Hirano T, Kishimoto T, Kaziro Y (1988) Induction of neuronal differentiation in PC12 cells by B-cell stimulatory factor-2/interleukin-6. Mol Cell Biol 8:3546–3550

    Google Scholar 

  90. Seckinger P, Williamson K, Balavoine JF, Mach B, Mazzei G, Shaw A, Dayer JM (1987) A urine inhibitor of interleukin 1 activity affects both interleukin 1 alpha and 1beta but not tumor necrosis factor alpha. J Immunol 139:1541–1545

    Google Scholar 

  91. Seckinger P, Lowenthal JW, Williamson K, Dayer JM, MacDonald HR (1987) A urine inhibitor of interleukin 1 activity that blocks ligand binding. J Immunol 139:1546–1549

    Google Scholar 

  92. Seckinger P, Isaaz S, Dayer JM (1988) A human inhibitor of tumor necrosis factor alpha. J Exp Med 167:1511–1516

    Google Scholar 

  93. Sehgal PB, Sagar AD (1980) Heterogeneity of poly(I) poly(C)-induced human fibroblast interferon mRNA species. Nature 288:95–97

    Google Scholar 

  94. Schgal PB, Zilberstein A, Ruggieri RM, May LT, Ferguson-Smith A, Slate DL, Revel M, Ruddle F (1986) Human chromosome 7 carries the β2 interferon gene. Proc Natl Acad Sci 83:5219–5222

    Google Scholar 

  95. Schgal PB, Walther Z, Tamm I (1987) Rapid enhancement of β2-interferon/B-cell differentiation factor BSF-2 gene expression in human fibroblasts by diacylglycerols and calcium ionophor A23187 Proc Natl Acad Sci USA 84:3663–3667

    Google Scholar 

  96. Sehgal PB, May LT, Tamm I, Vilcek J (1987) Human β2 interferon and B cell differentiation factor BSF-2 are identical. Science 235:731–732

    Google Scholar 

  97. Sehgal PB, Helfgott DC, Santhanam U, Tatter SB, Clarick RH, Ghrayeb J, May LT (1988) Regulation of the acute phase and immune responses in viral disease. J Exp Med 167:1951–1956

    Google Scholar 

  98. Shenkin A, Fraser WD, Series I, Winstanley FP, McCartney AC, Burns HJG, Van Damme I (1989) The serum interleukin 6 response to elective surgery. Lymphokine Res 8:123–127

    Google Scholar 

  99. Siegall CB, Chaudharyy Vk, Fitzgerald DJ, Pastan I (1988) Cytotoxic activity of an interleukin 6-Pseudomonas exotoxin fusion protein on human myeloma cells. Proc Natl Acad Sci 85:9738–9742

    Google Scholar 

  100. Simpson RJ, Moritz RL, Rubira MR, Van Snick J (1988) Murine hybridoma/plasmocytoma growth factor. Eur J Biochem 176:187–197

    Google Scholar 

  101. Sironi M, Breviario F, Proserpio P, Biondi A, Vecchi A, Van Damme J, Dejana E, Mantovani A (1989) IL-1 stimulates IL-6 production in endothelial cells. J Immunol 142:549–553

    Google Scholar 

  102. Suzuki C, Okano A, Takatsuki F, Miyasaka Y, Hirano T, Kishimoto T, Ejima D, Akiyama Y (1989) Continuous perfusion with interleukin 6 enhances production of hematopoietic stem cells (CFU-S). Biochem Biophys Res Commun 159:933–938

    Google Scholar 

  103. Tabibzadeh SS, Santhanam U, Sehgal PB, May LT (1989) Cytokine-induced production of IFNβ2/IL-6 by freshly explanted human endometrial cells. J Immunol 142:3134–3139

    Google Scholar 

  104. Takai Y, Wong GC, Clark SC, Burakoff SJ, Hermann SH (1988) B cell stimulatory factor 2 is involved in the differentiation of cytotoxic T lymphocytes. J Immunol 140:508–512

    Google Scholar 

  105. Takatsuki F, Okano A, Suzuki C, Chieda R, Takahara Y, Hirano T, Kishimoto T, Hamuro J, Akiyama Y (1988) Human recombinant IL-6/B cell stimulatory factor 2 augments murine antigen-specific antibody responses in vitro and in vivo. J Immunol 141:3072–3077

    Google Scholar 

  106. Tonouchi N, Oouchi N, Kashima N, Kawai M, Nagase K, Okano A, Matsui H, Yamada K, Hirano T, Kishimoto T (1988) High-level expression of human BSF-2/IL-6 cDNA in Escherichia coli using a new type of expression-preparation system. J Biochem 104:30–35

    Google Scholar 

  107. Tosato G, Gerrard TL, Goldman NG, Pike SE (1988) Stimulation of EBV-activated human B cells by monocytes and monocyte products. J Immunol 140:4329–4336

    Google Scholar 

  108. Tovey MG, Content J, Gresser I, Gugenheim J, Blanchard B, Guymarho J, Poupart P, Gigou M, Shaw A, Fiers W (1988) Genes for IFN-β-2 (IL-6), tumor necrosis factor, and IL-1 are expressed at high levels in the organs of normal individuals. J Immunol 141:3106–3110

    Google Scholar 

  109. Turner M, Feldman M (1988) Comparison of patterns of expression of tumor necrosis factor, lymphotoxin and interleukin-6 mRNA. Biochem Biophys Res Commun 153:1144–1151

    Google Scholar 

  110. Uyttenhove C, Coulie PG, Van Snick J (1988) T cell growth and differentiation induced by interleukin HP 1/IL-6. J Exp Med 167:1417–1427

    Google Scholar 

  111. Van Damme J, De Ley M, Van Snick J, Dinarello CA, Billiau A (1987) The role of interferonβ1 and the 26-kDa protein (interferonβ2) as mediators of the antiviral effects of interleukin1 and tumor necrosis factor. J Immunol 139:1867–1872

    Google Scholar 

  112. Van Damme J, Opdenakker G, Simpson RJ, Rubira MR, Cayphas S, Vink A, Billiau A, Van Snick J (1987) Identification of the human 26-kD protein, interferonβ2, as a B cell hybridoma/plasmocytoma growth factor induced by interleukin1 and tumor necrosis factor. J Exp Med 165:914–919

    Google Scholar 

  113. Van Damme J, Cayphas S, Van Snick J, Conings R, Put W, Lenaerts JP, Simpson RJ, Billiau A (1987) Purification and characterization of human fibroblast-derived hybridoma growth factor identical to T-cell-derived B-cell stimulatory factor-2 (interleukin-6). Eur J Biochem 168:543–550

    Google Scholar 

  114. Van Damme J, Cayphas S, Opdenakker G, Billiau A, Van Snick J (1987) Interleukin 1 and poly(rI)·poly(rC) induce production of a hybridoma growth factor by human fibroblasts. Eur J Immunol 17:1–17

    Google Scholar 

  115. Van Damme J, Van Beeumen J, Decock B, Van Snick J, De Ley M, Billiau A (1988) Separation and comparison of two monokines with lymphocyte-activating factor activity: IL-1β and hybridoma growth factor (HGF). J Immunol 140:1534–1541

    Google Scholar 

  116. Van Damme J, Schaafsma MR, Fibbe WE, Falkenburg JHF, Opdenakker G, Biliau A (1989) Simultaneous production of interleukin 6, interferon and colony-stimulating activity by fibroblasts after viral and bacterial infection. Eur J Immunol 19:163–168

    Google Scholar 

  117. Van Oers MHJ, Van der Heyden AAPAM, Aarden LA (1988) Interleukin 6 (IL-6) in serum and urine of renal transplant recipients. Clin Exp Immunol 71:314–319

    Google Scholar 

  118. Van Snick J, Cayphas S, Vink A, Uyttenhove C, Coulie PG, Rubira M, Simpson J (1986) Purification and NH2-terminal amino acid sequence of a T-cell-derived lymphokine with growth factor activity for B-cell hybridomas. Proc Natl Acad Sci USA 83:9679

    Google Scholar 

  119. Van Snick J, Vink A, Cayphas S, Uyttenhove C (1987) Interleukin-HP1, a T-cell-derived hybridoma growth factor that supports the in vitro growth of murine plasmocytomas. J Exp Med 165:641

    Google Scholar 

  120. Vaquero C, Sanceau J, Weissenbach J, Beranger F, Falcoff R (1986) Regulation of human gamma-interferon and beta-interferon gene expression in PHA-activated lymphocytes. J Interferon Res 6:161–170

    Google Scholar 

  121. Weissenbach J, Chernajovsky Y, Zeevi M, Shulman L, Soreq H, Nir U, Wallach D, Perricaudet M, Tiollais P, Revel M (1980) Two interferon mRNAs in human fibroblasts: In vitro translation and Escherichia coli cloning studies. Proc Natl Acad Sci USA 77:7152–7156

    Google Scholar 

  122. Woloski BMRNJ, Fuller GM (1985) Identification and partial characterization of hepatocyte-stimulating factor from leukemia cell lines: comparison with interleukin 1. Proc Natl Acad Sci 82:1443–1447

    Google Scholar 

  123. Woloski BMRNJ, Smith EM, Meyer WJ, Fuller GM, Blalock JE (1985) Corticotropin-releasing activity of monokines. Science 230:1035–1037

    Google Scholar 

  124. Wong GG, Witek JAS, Temple PA, Kriz R, Ferenz C, Hewick RM, Clark SC, Ikebuchi K, Ogawa M (1988) Stimulation of murine hematopoietic colony formation by human interleukin-6. J Immunol 140:3040–45

    Google Scholar 

  125. Yamasaki K, Taga T, Hirata Y, Yawata H, Kawanishi Y, Seed B, Taniguchi T, Hirano T, Kishimoto T (1988) Cloning and expression of the human interleukin-6 (BSF-2/IFNβ2) receptor. Science 241:825–828

    Google Scholar 

  126. Yasukawa K, Hirano T, Watanabe Y, Muratani K, Matsuda T, Nakai S, Kishimoto T (1987) Structure and expression of human B cell stimulatory factor-2 (BSF-2/IL-6) gene. EMBO J 6:2939–2945

    Google Scholar 

  127. Zhang Y, Lin JX, Yip YK, Vilcek J (1988) Enhancement of cAMP levels and of protein kinase activity by tumor necrosis factor and interleukin 1 in human fibroblasts: Role in the induction of interleukin 6. Proc Natl Acad Sci USA 85:6802–6805

    Google Scholar 

  128. Zilberstein A, Ruggieri R, Korn JH, Revel M (1986) Structure and expression of cDNA and genes for human interferon-beta-2, a distinct species inducible by growth-stimulatory cytokines. EMBO J 5:2529–2537

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medizinische Universitätsklinik, Universität Freiburg im Breisgau, Germany

    J. Bauer

Authors
  1. J. Bauer
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Dedicated to Hedwig

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bauer, J. Interleukin-6 and its receptor during homeostasis, inflammation, and tumor growth. Klin Wochenschr 67, 697–706 (1989). https://doi.org/10.1007/BF01721287

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01721287

Key words

Search

Navigation