Inhibitory action of cyclosporin A on the early events of T cell activation: effects on T cell-independent production of IL1 and on IL1-dependent expression of reactivity to IL2.

Cyclosporin A (CsA) has a selective immunosuppressive effect on T cell functions, but its mode of action on IL1 activities and production remain unclear and controversial. While it has been documented that CsA has a profound effect on the ability of IL1 to promote IL2 production, its effects on the ability of IL1 to promote IL2-responsiveness are not known. Macrophage-depleted nylon wool non-adherent thymocytes (NATs) were preincubated for 6 h with or without IL1 in the presence of a wide range of concentrations of CsA (1 ng/ml-1 microgram/ml), washed and then pulsed with Con A. After washings in medium with alpha-MM, the capacity of NATs to proliferate in response to IL2 was determined. Both background and IL1-dependent acquisition of IL2-reactivity were inhibited by concentrations of CsA as low as 5 ng/ml. The effects of CsA (1 ng/ml-1 microgram/ml) on T cell-independent production of IL1 by irradiated, carrageenan-stimulated peritoneal macrophages were also examined. Up to 50 ng/ml CsA had no effect on IL1 production but higher concentrations produced a dose-dependent inhibition that was complete at 1 microgram/ml. These results show that CsA inhibits both T cell-independent production of IL1 and IL1-dependent expression of reactivity to IL2.