Induction of IL-5 expression by IL-2 is resistant to the immunosuppressive agents cyclosporin A and rapamycin

T cell cytokine expression may be induced by the cytokine IL-2 or via theTCR complex. The comparative effects of cytokine- and TCR-mediatedsignalling on the induction of human IL-5 mRNA were examined. Cytokine mRNAexpression was analysed by RT-PCR in fresh peripheral blood mononuclearcells (PBMC) from normal individuals and in populations of activated Tlymphocytes, derived from phytohaemagglutinin (PHA)- stimulated PBMC. rIL-2induced IL-5 expression in PBMC, the kinetics of which were similar to theeffects of PHA. rIL-4 induced IL-5 mRNA expression in activated Tlymphocytes. IL-5 expression induced by either IL-2 or PHA was completelyabolished by the protein synthesis inhibitor cycloheximide. rIL-2-inducedIL-5 expression was resistant to cyclosporin A (CsA), whereas IL-5expression elicited by PHA was inhibited by CsA, at doses as low as 10ng/ml. Rapamycin (RAP) had no effect on rIL-2-stimulated IL-5 expression,but suppressed IL-5 expression induced by PHA. The inhibitory effect of RAPon PHA-induced IL-5 expression was more apparent at 12 and 24 h afterstimulation than at earlier times. The resistance of IL-2 receptor (IL-2R)signalling to CsA and RAP indicates that the IL-2R and the TCR areassociated with different pathways regulating IL-5 expression.