123. Corticosteroids, but not catecholamines, mediate stress- and surgery-induced suppression of plasma IL-12 levels in rats: A second-phase response of stress-induced immune perturbations

Abstract

We recently reported that various stress paradigms suppress plasma IL-12 levels. The aim of this study was to elucidate potential neuroendocrine mediating mechanisms. Administration of prostaglandin-E2, epinephrine, and corticosterone, significantly reduced plasma IL-12 levels. However, when subjecting animals to stress or surgery, only the glucocorticoid-receptor blocker, mifepristone, and the COX-2 inhibitor, etodolac, but not α- or β-adrenergic blockers, attenuated the reduction of plasma IL-12 levels. As epinephrine administration did reduce IL-12 levels, we subjected adrenalectomized and sham-operated rats to epinephrine and/or corticosterone administration. While corticosterone reduced IL-12 levels in both conditions, epinephrine did so only in sham operated animals, indicating that its effects are mediated through elevated endogenous corticosterone levels, which we confirmed. In addition, blockade of prostaglandin production during surgery also reduced corticosterone levels, suggesting that at least some of the effects of prostaglandin are corticosterone-mediated. In accordance, but contrary to some reports, our in vitro studies indicated that corticosterone, but not prostaglandin-E2 or epinephrine, reduced spontaneous and induced IL-12 production levels. We thus hypothesize that stress-induced immune perturbations rely on two mechanisms: One mediated through activation of short-lasting processes by catecholamines and/or prostaglandins, and a second leading to long-lasting perturbations through glucocorticoids. IL-12 has a long half-life time and is prominent in inducing Th1 differentiation – a long lasting process that, as observed herein, is indeed suppressed through elevated corticosteroids, but not catecholamines.