Effects of cyclosporin A (CyA) and methylprednisolone (MP) on the immune response. II. Further studies of the monocyte - T cell interactions leading to lymphokine production.

The immunosuppressive drugs cyclosporin A (CyA) and methylprednisolone (MP) abolished the elaboration of the lymphokine leukocyte migration inhibitory factor (LIF) by mononuclear cells challenged by recall antigen. Suppression in both cases was reversible upon removal of the drugs, and participation of T suppressor cells of their mediators could not be demonstrated. The CyA-induced effect was exerted in the early stage of lymphocyte activation (less than 60 min), whereas MP still inhibited LIF release when added 60 min after the antigen. In contrast to earlier findings that the drugs failed to affect the release of T cell-activating factor (TAF) and lymphocyte-activating factor (LAF) from macrophages (M-phi's) stimulated by phorbol myristate acetate. MP (but not CyA) markedly reduced TAF production by M-phi's incubated with tuberculin. M-phireover, partially purified TAF and LAF both restored LIF production in the presence of CyA (but not MP), an effect not mimicked by the T cell product T cell growth factor. However, suppression by both drugs was abrogated by exogenous cGMP. Hence, CyA seems to obstruct the interaction between TAF/LAF and the immune T cell, whereas MP affects antigen-induced T cell activation at the Mo level as well as the level of lymphokine production and/or release. The effects of both drugs seem related to intracellular events involving cGMP.