Inhibition of cytokine production by cyclosporin A and transforming growth factor beta.
We investigated the ability of cyclosporin A (CsA) and transforming growth factor beta (TGF-beta) to modulate the production of TNF-alpha and TNF-beta and IFN-gamma by unseparated, nonadherent, and adherent PBMC. Treatment of unseparated PBMC with CsA resulted in a significant dose-dependent inhibition of all three cytokines ranging from greater than 90% inhibition for IFN-gamma and TNF-beta, to approximately 70% for TNF-alpha. Pretreatment of unseparated or nonadherent PBMC with TGF-beta inhibited the production of IFN-gamma by 60-70%. However, the inhibition of TNF-alpha and TNF-beta production by these cells was only minimally affected, and at 0.1-1 ng/ml TGF-beta could enhance TNF-alpha production by unseparated PBMC. In contrast, pretreatment of adherent PBMC with TGF-beta inhibited the production of TNF-alpha by approximately 60%. TGF-beta also inhibited both TNF-alpha production and tumor cell cytotoxicity mediated by murine peritoneal-derived macrophages. These observations indicate that the biological effects of CsA and TGF-beta on immune functions are of a wider range than previously reported.
D000818:Animals; D001688:Biological Products / Q000096:biosynthesis*; D003524:Cyclosporins / Q000494:pharmacology*; D016207:Cytokines; D004305:Dose-Response Relationship, Drug; D005260:Female; D006023:Glycoproteins / Q000096:biosynthesis; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000494:pharmacology*; D015291:Transforming Growth Factors; D014409:Tumor Necrosis Factor-alpha
D001688:Biological Products; D003524:Cyclosporins; D016207:Cytokines; D006023:Glycoproteins; D006133:Growth Substances; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; D015291:Transforming Growth Factors; D007371:Interferon-gamma