Interleukin-2 effect on the inhibition of mixed lymphocyte reaction induced by cyclosporin A.

Cyclosporin A (CsA) was found to have remarkable immune suppressive properties without the usual significant myelotoxicity and to be a clinically very useful agent to prevent rejection of organ transplantation or bone marrow transplantation graft-versus-host disease in recently. The inhibitory effect of CsA on the production of interleukin-2 (IL-2) has been implicated as a major reason accounting for CsA mediated immunosuppression. But the exact mode of its immunosuppressive effect remains unclear. We studied the influence of CsA and exogenous IL-2 on the proliferative response in allogeneic mixed lymphocyte culture. The results were as follows: 1. There is apparent inhibition of proliferative response in mixed lymphocyte reaction (MLR) by CsA in a dose-dependent manner, where optimal concentration is approximately 0.5 ug∼1.0 ug/ml. 2. The time-course sequential studies indicated that the lymphocyte response was markedly dependent on the time of addition of CsA to the culture ongoing MLR, the inhibitory effect of proliferative response by CsA was markedly abolished after 20 hours of the culture (Mean cpm 12,578±1,445/28,324±319). 3. At the beginning of the MLR, an addition of both CsA and exogenous IL-2 (human, 2.0 U/ml) was found to have no appreciable immunosuppressive effect. 4. Exogenous human IL-2 abolished the CsA effect on the MLR but mouse IL-2 could not.