Resistance of central nervous system interleukin-6 to glucocorticoid inhibition in monkeys

The ability of both exogenous and endogenous glucocorticoids (GCs) to inhibit proinflammatory cytokine production was investigated in vivo. Specifically, we investigated the effects of elevated GC levels on interleukin (IL)-1-induced release of IL-6 into both blood and cerebrospinal fluid (CSF). Three experiments were conducted in rhesus macaques to elevate corticoid levels for at least 4 h before administration of IL-1beta. The first study used dexamethasone pretreatment, the second utilized ACTH to stimulate endogenous cortisol release, while the third relied on a psychological challenge to stimulate the hypothalamic-pituitary-adrenal axis. Contrary to our a priori predictions, none of these treatments attenuated the IL-1-induced release of IL-6 into CSF. Additionally, the pattern in the blood response was similar, such that the IL-6 response was not blocked, although there was a trend toward a reduction of this response. These data indicated that the IL-1-induced IL-6 response is for the most part resistant to corticosteroid influence, such that even when a partial inhibition was sometimes evident in blood, cytokine release in the central nervous system was not affected.