Effects of immunosuppressive drugs on functions of activated T lymphocytes. Cyclosporine inhibition of gamma interferon production in the presence of interleukin.
Expression of HLA DR by tubular cells of renal allografts of patients treated with cyclosporine (CsA) is less than that from patients treated with a combination of methylprednisolone (MPRED) and azathioprine (AZA). To examine the reason for this difference, the effects of immunosuppressive drugs on functions of alloactivated mononuclear cells, which had been primed in culture without added immunosuppressive drugs, was compared. CsA, 0.1 microgram/ml, inhibited gamma interferon production by 79 +/- 7% and in the presence of interleukin 2 (IL-2) by 82 +/- 10%. CsA, 0.1 microgram/ml, inhibited cytotoxic effector function by 11 +/- 12% and proliferation of cells that had been washed to remove lymphokines by 61 +/- 17% but only 17 +/- 8% in the presence of IL-2. MPRED, 20 micrograms/ml, inhibited gamma interferon production by washed alloactivated cells by 79 +/- 12% and 59 +/- 7% with IL-2. MPRED, 20 micrograms/ml, inhibited proliferation of washed cells by 36 +/- 4 and 86 +/- 3% with or without IL-2, respectively, and it inhibited cytotoxic effector function by 71 +/- 16%. AZA and its metabolites 6-mercaptopurine and 6-thioinosinic acid had little inhibitory effect on any tested function of activated lymphocytes at a concentration of 0.2 microgram/ml. These results indicate that CsA has a greater inhibitory effect on gamma interferon production by activated lymphocytes in the presence of IL-2 than MPRED or AZA in vitro, which may explain their differential effects on renal tubular cell HLA DR expression in vivo. Gamma interferon production was the only activated lymphocyte function tested that was inhibited by CsA in the presence of IL-2. MPRED was able to inhibit all functions, albeit to a lesser degree, in the presence of IL-2 or of IL-2-containing culture supernatants.
D001379:Azathioprine / Q000494:pharmacology; D003524:Cyclosporins / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008775:Methylprednisolone / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology*
D003524:Cyclosporins; D006684:HLA-DR Antigens; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D007371:Interferon-gamma; D001379:Azathioprine; D008775:Methylprednisolone