Different susceptibilities to cyclosporin A of the mitogenic and potentiating activities of interleukins.
A dissociation was observed between the mitogenic and potentiating activities of interleukins (ILs)-1 or -2 in murine thymocyte cultures treated with drugs. The direct mitogenic effects of the ILs were unaffected by cyclosporin A (CsA) at concentrations which abolished the potentiating activities of these mediators, i.e. their synergy with lectins. Conversely to CsA, dexamethasone was more inhibitory to the mitogenic activity of the ILs than to their synergistic reactions with the lectins. The resistance to CsA of the mitogenic activity of IL-1 was unexpected since this response is assumed to be mediated by newly formed IL-2 and CsA inhibits IL-2 production. This resistance was further tested by coculturing thymocytes with the IL-2-dependent CT6 cells; net gains of thymidine uptake by the cocultures were attributed to IL-2 release. Such net gains were observed in cocultures stimulated with IL-1 alone and were relatively resistant to CsA. On the other hand, net gains stimulated by mitogenic lectins, alone or with IL-1, were eliminated by CsA. These results support the notion that IL-1 direct activity on thymocytes is mediated by newly released IL-2 and show that this IL-1 activity is unusual in being resistant to CsA. Low levels of protection against CsA were also observed in cultures potentiated by IL-1: lymphocytes stimulated by lectins or antigens and IL-1 were inhibited by CsA less than lymphocytes stimulated without IL-1. Yet, this partial protection by IL-1 was achieved only at CsA concentrations about 100 fold lower than those resisted by thymocytes directly stimulated by IL-1.
D000276:Adjuvants, Immunologic / Q000502:physiology*; D000818:Animals; D002460:Cell Line; D003524:Cyclosporins / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D007375:Interleukin-1 / Q000502:physiology*; D007376:Interleukin-2 / Q000502:physiology*; D037102:Lectins / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008808:Mice, Inbred CBA; D013601:T-Lymphocytes / Q000276:immunology
D000276:Adjuvants, Immunologic; D003524:Cyclosporins; D007375:Interleukin-1; D007376:Interleukin-2; D037102:Lectins; D003907:Dexamethasone