Reversal of the effects of cyclosporin A on the production of human interferon-gamma.

Previous reports have documented that cyclosporin A (CsA) can inhibit the production of interferon-gamma (HuIFN-gamma) and interleukin-2 (IL-2). In this report we have extended these earlier findings and have demonstrated that the defect in the production of HuIFN-gamma persists even after the CsA is removed and is associated with altered synthesis of other lymphokines, mainly a cytotoxin and leukocyte migration inhibition factor. In the presence of recombinant exogenous IL-2, the effect of CsA on the synthesis of HuIFN-gamma can be reversed depending on the concentrations of both the IL-2 and CsA. In addition, the presence of the calcium ionophore A23187 partially reverses the inhibitory effect of CsA by synergistically enhancing the synthesis of HuIFN-gamma.