, Volume 3, Issue 2, pp 127–133 | Cite as

Immunomodulatory effect of tumor necrosis factor

  • Benjamin Bonavida

Key words

B cell cytokines immunoglobulin macrophages modulation regulation T cell 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Bonavida B, Gifford GE, Kirchier H, eds. Tumor necrosis factor/cachectin and related cytokines. Basel: Karger, 1988.Google Scholar
  2. 2.
    Bonavida B, Granger G, eds. Tumor necrosis factor: structure, mechanism of action, role in disease and therapy. Basel: Karger, 1990.Google Scholar
  3. 3.
    Pennica D, Nedwin GE, Hayflick JS. Human tumor necrosis factor: precursor structure, expression and homology to lymphotoxin. Nature (London) 1984; 312: 724–9.Google Scholar
  4. 4.
    Kriegler M, Perez C, Dekay K. A novel form of TNF/ Cachectin is a cell surface cytotoxic transmembrane protein. Ramifications for the complex physiology of TNF. Cell 1988; 53: 45–53.PubMedGoogle Scholar
  5. 5.
    Smith RA, Baglioni C. The active form of tumor necrosis factor is a trimer. J Biol Chem 1987; 262: 6951–4.PubMedGoogle Scholar
  6. 6.
    Jones EY, Stuart DI, Walker NPC. Structure of tumor necrosis factor. Nature 1989; 338: 225–8.PubMedGoogle Scholar
  7. 7.
    Beutler B, Cerami A. Cachectin and tumor necrosis factor as two sides of the same biological coin. Nature 1986; 320: 584–8.PubMedGoogle Scholar
  8. 8.
    Urban JL, Shepard HM, Rothstein JL, Sugarman BJ, Schreiber H. Tumor necrosis factor: a potent effector molecule for tumor cell killing by activated macrophages. Proc Natl Acd Sci USA 1986; 83: 5233–7.Google Scholar
  9. 9.
    Degliantoni G, Murphy M, Kobayashi M. 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 1986; 162: 1512–30.Google Scholar
  10. 10.
    Pawelec G, Sachandt K, Rehlein A, Busch FW. Differential secretion of tumor necrosis factorα and granulocyte/ macrophage colony stimulating factor but not interferon-γ from CD4+ compared to CD8+ human T cell clones. Eur J Immunol 1989; 19: 197–200.PubMedGoogle Scholar
  11. 11.
    Cherwinski HM, Schumacher JH, Brown KP, Mosmann TR. Two types of mouse helper T cells clones. II. Further differences in lymphokine synthesis between TH1 and TH2 clones revealed by RNA hybridization, functionally monospecific bioassays, and monoclonal antibodies. J Exp Med 1982; 166: 1229–44.Google Scholar
  12. 12.
    Dinarello CA, Cannon JG, Wolff SM. Tumor necrosis factor (cachectin) is an endogenous pyrogen and induces production of interleukin-1. J Exp Med 1986; 163: 1433–50.PubMedGoogle Scholar
  13. 13.
    Scheurich P, Thomas B. Ucer: immunoregulatory activity of recombinant human tumor necrosis factor (TNF)-α: induction of TNF receptors on human T cells and TNF-α mediated enhancement of T cell responses. J Immunol 1987; 138: 1786–90.PubMedGoogle Scholar
  14. 14.
    Yokota S, Geppert TD, Lipsky PE. Enhancement of antigen- and mitogen-induced human T lymphocyte proliferation by tumor necrosis factor-α. J Immunol 1988; 140: 531–6.PubMedGoogle Scholar
  15. 15.
    Vine JB, Geppert TD, Lipsky PE. T4 cell activation by immobilized PHA: differential capacity to induce IL-2 responsiveness and IL-2 production. J Immunol 1988; 141: 2593–600.PubMedGoogle Scholar
  16. 16.
    Ranges GE, Zlotnick A, Espevick T, Dinarello CA. Tumor necrosis factorα/cachectin is a growth factor for thymocytes. Synergistic interactions with other cytokines. J Exp Med 1988; 167: 1472–8.PubMedGoogle Scholar
  17. 17.
    Jelinek DF, Lipsky PE. Enhancement of human B cell proliferation and differentiation by tumor necrosis factora and interleukin-1. J Immunol 1987; 139: 2970–6.PubMedGoogle Scholar
  18. 18.
    Kehrl JH, Miller A, Fauci AS. Effect of tumor necrosis factor-α on mitogen-activated human B cells. J Exp Med 1987; 166: 786–91.PubMedGoogle Scholar
  19. 19.
    Kashiwa H, Wright SC, Bonavida B. Regulation of B cell activation and differentiation I. Suppression of pokeweed mitogen induced B cell differentiation by tumor necrosis factor (TNF). J Immunol 1987; 138: 1383–90.PubMedGoogle Scholar
  20. 20.
    Waldmann TA, Broder S. Polyclonal B cell activators in the study of regulation of immunoglobulin synthesis in the human system. Adv Immunol 1982; 32: 1–63.PubMedGoogle Scholar
  21. 21.
    Kashiwa H, Bonavida B. Regulation of B cell activation and differentiation II. Immunosuppressive role of endogenously produced TNFα in PWM stimulated polyclonal Ig PFC response. (Submitted)Google Scholar
  22. 22.
    Kashiwa H, Bonavida B. Regulation of B cell activation and differentiation III. Restoration by interferon gamma of TNF-β mediated suppression of human B cell differentiation into Ig producing cells. (Submitted)Google Scholar
  23. 23.
    Brunswick M, Lake P. Obligatory role of gamma interferon in T cell replacing factor-dependent antigen specific on murine B cell response. J Exp Med 1985; 161: 953–71.PubMedGoogle Scholar
  24. 24.
    Kehrl JH, Alvarez Mon M, Delsinge GA, Fauci AS. Lymphotoxin is an important T cell derived growth factor for human B cells. Science 1982; 238: 1144–6.Google Scholar
  25. 25.
    Zola H, Nikoloutsopoulos A. Effect of recombinant human tumor necrosis factor beta (TNFβ) on activation, proliferation and differentiation of human B lymphocytes. Immunology 1989; 67: 231–6.PubMedGoogle Scholar
  26. 26.
    Phillips R, Epstein LB. Tumor Necrosis Factor as immunomodulator and mediator of monocyte cytotoxicity induced by itself, gamma interferon and interleukin-1. Nature 1986; 323: 86–9.PubMedGoogle Scholar
  27. 27.
    Fiers W, Beyaert R, Bronkaert P.In vitro andin vivo action of tumor necrosis factor. In: Bonavida B, Granger G, eds. Tumor necrosis factor: structure, mechanism of action, role in disease and therapy. Basel: Karger, 1990: 77–81.Google Scholar
  28. 28.
    Aderka D, Reis LFL, Lee TK. Interleukin-6; a cytokine induced by TNF, and once thought to mediate the antiviral action of TNF, inhibits TNF production in monocytes and U937 cells primed with GM-CSF. In: Bonavida B, Granger G, eds. Tumor necrosis factor: structure, mechanism of action, role in disease and therapy. Basel: Karger, 1990: 133–9.Google Scholar
  29. 29.
    Munker R, Gasson J, Ogawa M. Recombinant human TNF induces production of granulocyte monocyte colony stimulating factor. Nature 1986; 323: 79–82.PubMedGoogle Scholar
  30. 30.
    Cannistra SA, Rambaldi A, Spriggs DR. Human granulocyte-macrophage colony stimulating factor induces expression of the tumor necrosis factor gene by the U937 cell line and by normal human monocytes. J Clin Inv 1988; 79: 1720–8.Google Scholar
  31. 31.
    Ichinose Y, Bakouche O, Tsao JY, Fidler IJ. Tumor necrosis factor and IL-1 associated with plasma membrane of a activated human monocytes lyse monokine-sensitive but not monokine resistant tumor cells whereas viable activated monocytes lyse both. J Immu 1988; 141: 512–8.Google Scholar
  32. 32.
    Patek PQ, Liu Y, Collins JL. Natural cytotoxic cells and tumor necrosis factor activate similar lytic mechanisms. J Immunol 1987; 138: 1641–6.PubMedGoogle Scholar
  33. 33.
    Epstein LB, Lackides GA, Smith DM. The complex relationship of tumor necrosis factor and interleukin-1β in human monocytes. In: Bonavida B, Granger G, eds. Tumor necrosis factor: structure, mechanism of action, role in disease and therapy. Basel: Karger, 1990; 107–13.Google Scholar
  34. 34.
    Bancroft GJ, Sheehan KCF, Schreiber RD, Unanue ER. Tumor necrosis factor is involved in the T cell dependent pathway of macrophage activation in Scid mice. J Immunol 1989; 143: 127–30.PubMedGoogle Scholar
  35. 35.
    Ostensen ME, Thiele DL, Lipsky PE. Tumor necrosis factor-α enhances cytolytic activity of human natural killer cells. J Immunol 1987; 138: 4185–91.PubMedGoogle Scholar
  36. 36.
    Hemmi H, Nakamura T, Tamua K. Lymphotoxin: induction of terminal differentiation of the human myeloid leukemia cell lines; HL-60 and THP-1. J Immunol 1987; 138: 664–6.PubMedGoogle Scholar
  37. 37.
    Trinchieri G, Kobayahi M, Rosen M. Tumor necrosis factor and lymphotoxin induce differentiation of human myeloid cells in synergy with immune interferon. J Exp Med 1986; 164: 1206–25.PubMedGoogle Scholar
  38. 38.
    Larrick JW, Kunchel SL. The role of tumor necrosis factor and interleukin in the immunoinflammatory response. Pharmaceutical Research 1988; 5: 129–39. (Review)PubMedGoogle Scholar
  39. 39.
    Beutler B, Milsark IW, Cerami AC. Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science 1985; 229: 869–71.PubMedGoogle Scholar
  40. 40.
    Galanos C, Freundenberg MA. Tumor necrosis factor mediates endotoxin shock: the protective effects of antibody and cortisone. In: Bonavida B, Granger G, eds. Tumor necrosis factor: structure, mechanism of action, role in disease and therapy. Basel: Karger, 1990: 187–93.Google Scholar

Copyright information

© Kluwer Academic Publishers 1991

Authors and Affiliations

  • Benjamin Bonavida
    • 1
  1. 1.Department of Microbiology and ImmunologyUCLA School of Medicine and the Jonsson Comprehensive Cancer Center, University of CaliforniaLos AngelesUSA

Personalised recommendations