Catecholamines mediate stress-induced increases in peripheral and central inflammatory cytokines

Proinflammatory cytokines act at receptors in the CNS to alter physiological and behavioral responses. Exposure to stressors increases both peripheral and central proinflammatory cytokines, yet the mechanism(s) of induction remain unknown. Experiments here examined the role of catecholamines in the in vivo induction of proinflammatory cytokines following tailshock stress. Rats were pretreated i.p. with 2.0 mg/kg prazosin (alpha(1)-adrenoceptor antagonist), 10.0 mg/kg propranolol (beta-adrenoceptor antagonist), or 5.0 mg/kg labetalol (alpha(1)- and beta-adrenoceptor antagonist) 30 min prior to tailshock exposure and plasma interleukin-1 beta (IL-1 beta) and IL-6, along with tissue interleukin-1beta from the hypothalamus, hippocampus, and pituitary were measured immediately following stressor termination. Prazosin attenuated stress-induced plasma IL-1 beta and IL-6, but had no effect on tissue IL-10 levels, while propranolol attenuated plasma IL-6 and blocked tissue IL-1 beta elevation, and labetalol, which cannot cross the blood-brain barrier, attenuated plasma IL-1 beta and IL-6, blocked pituitary IL-1 beta, but had no effect on central tissue IL-10 levels. Furthermore, administration of 50.0 mg/kg N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride, a neurotoxin that lesions neural projections from the locus coeruleus, prevented stress-induced elevation in hippocampal IL-1 beta, a region highly innervated by the locus coeruleus, but had no effect on hypothalamic IL-1 beta, a region that receives few locus coeruleus projections. Finally, i.p. injection of 5.0 mg/kg isoproterenol (beta-adrenoceptor agonist) was sufficient to induce circulating IL-1 and IL-6, and tissue IL-1 beta. These data suggest catecholamines play an important role in the induction of stress-induced proinflammatory cytokines and that beta-adrenoceptors are critical for tissue IL-1 beta induction, while both alpha- and beta-adrenoceptors contribute to the induction of plasma cytokines. (c) 2005 Published by Elsevier Ltd on behalf of IBRO.