Effect of interleukin 2, interferon-gamma, and mitogens on the production of tumor necrosis factors alpha and beta.
Human peripheral blood mononuclear cells (PBMC) were induced by recombinant interleukin 2 and mitogens to secrete two distinct cytotoxic polypeptides, tumor necrosis factor-alpha (TNF-alpha) and tumor necrosis factor-beta (TNF-beta), previously called lymphotoxin. Treatment of PBMC with recombinant human interleukin 2 (rIL 2) or mitogens in combination with recombinant human interferon-gamma (rIFN-gamma) resulted in augmented production of both TNF-alpha and TNF-beta. rIFN-gamma alone had no effect on production of either cytotoxic polypeptide. TNF-alpha was produced within 2 to 3 hr after induction and was the major cytotoxin produced by PBMC during the first 48 hr of culture, after which time TNF-beta became the predominant species. TNF-beta was first secreted into the media after 8 hr of induction. Enhanced levels of both TNF-alpha and TNF-beta were seen when the PBMC were separated into adherent and nonadherent cells. Both TNF-alpha and TNF-beta were induced in different tumor cell lines of hematopoietic origin. The results demonstrate that the production of TNF-alpha and TNF-beta can be enhanced by two lymphokines, IL 2 and IFN-gamma.
D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D006023:Glycoproteins / Q000096:biosynthesis* / Q000502:physiology; D006131:Growth Inhibitors / Q000096:biosynthesis* / Q000502:physiology; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology*; D007376:Interleukin-2 / Q000502:physiology*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000145:classification / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008934:Mitogens / Q000494:pharmacology*; D014411:Neoplastic Stem Cells / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha
D006023:Glycoproteins; D006131:Growth Inhibitors; D007376:Interleukin-2; D008934:Mitogens; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma