Significance of enhanced cytokine receptor expression by glucocorticoids

Abstract

As antiproliferative agents, glucocorticoids (GCs) exert their effects by several mechanisms, the most significant of which being inhibition of cytokine production and action.1 In addition, GCs upregulate the expression of select proinflammatory cytokine receptors directly or indirectly in association with growth factors or other factors,2,3 thereby augmenting cytokine effects on target cells. This enhancement of cytokine receptor was specific for the GCs, required de novo receptor synthesis, and resulted in increased receptor density but not affinity.4,5 However, the effect of GCs on interleukin-2 receptor (IL-2R) remain controversial, because they were shown to either inhibit IL-2Rα6 or enhance high-affinity IL-2R directly or indirectly in association with IL-2,3 thus raising the possibility that the reduction in IL-2Rα expression may be due to earlier blockade of IL-2 synthesis by GCs. Furthermore, it was reported that GCs may decrease or increase IL-2R expression and hence the response to IL-2 stimulation depending on the extent of T-cell activation.7 The effect of GCs on IL-2R must then be viewed in the context of direct effect of GCs on IL-2R and the contribution of IL-2 blockade by GCs on subsequent IL-2R expression.