Effect of cyclosporin A (CyA) on the immune response. CyA competitively inhibits the function of monocyte/macrophage-derived T-lymphocyte-activating factor(s).
The mechanism of action of the immunosuppressive drug, cyclosporin A (CyA), was analyzed with respect to antigen-induced production of the human lymphokine, leukocyte migration inhibitory factor (LIF). Mononuclear cells as well as purified T-cells did not elaborate LIF in the presence of pharmacological concentrations of CyA. CyA-induced immunosuppression was competitively reversed by addition of the partially purified monokines, T-cell-activating factor (TAF) and lymphocyte-activating factor (LAF). CyA did not affect T-cell priming with antigens. The drug failed to abolish LIF production if added 60 min after challenge of T-cells with recall antigen in the presence of TAF. Furthermore, addition of TAF within 15 min to CyA-treated T-cells resulted in unaltered LIF production. These results suggest that CyA suppresses the early stage of the immune response by competing with the function of TAF/LAF on the immune T-cell.
D000328:Adult; D001667:Binding, Competitive; D003524:Cyclosporins / Q000494:pharmacology*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007375:Interleukin-1 / Q000096:biosynthesis / Q000494:pharmacology*; D007961:Leukocyte Migration-Inhibitory Factors / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D013997:Time Factors
D003524:Cyclosporins; D007166:Immunosuppressive Agents; D007375:Interleukin-1; D007961:Leukocyte Migration-Inhibitory Factors