A comparison of the effects of cyclosporin A, dexamethasone, and ouabain on the interleukin-2 cascade.

We have studied the mechanism by which cyclosporin A (CsA), dexamethasone (DEX), and ouabain (OUA) inhibit T cell proliferation by measuring the effects of these agents on 1) interleukin-2 (IL-2) production, 2) acquisition of IL-2 responsiveness, 3) the induction of IL-2 receptor expression, and 4) the specific interaction of IL-2 with its receptor. DEX primarily inhibited IL-2 production and did not block acquisition of responsiveness to IL-2 or interaction of IL-2 with its receptor. OUA mainly interfered with the mitogenic activity of IL-2 on IL-2 dependent cells and showed a modest inhibitory effect on IL-2 production. In contrast, CsA blocked acquisition of responsiveness of resting T cells to IL-2, inhibited IL-2 production, and also inhibited IL-2 receptor expression at 48 hrs but not at 24 hrs following mitogen stimulation. The protocol described in these studies should prove to be useful in dissecting the mechanisms responsible for the depressed lymphoproliferative responses in different autoimmune and immunodeficiency disease states.