Molly Nickerson

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 (alpha1-adrenoceptor antagonist), 10.0 mg/kg propranolol (beta-adrenoceptor antagonist), or 5.0 mg/kg labetalol (alpha1- and beta-adrenoceptor antagonist) 30 min prior to tailshock exposure and plasma interleukin-1beta (IL-1beta) 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-1beta and IL-6, but had no effect on tissue IL-1beta levels, while propranolol attenuated plasma IL-6 and blocked tissue IL-1beta elevation, and labetalol, which cannot cross the blood-brain barrier, attenuated plasma IL-1beta and IL-6, blocked pituitary IL-1beta, but had no effect on central tissue IL-1beta 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-1beta, a region highly innervated by the locus coeruleus, but had no effect on hypothalamic IL-1beta, 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-1beta. 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-1beta induction, while both alpha- and beta-adrenoceptors contribute to the induction of plasma cytokines.

Splenic norepinephrine depletion following acute stress suppresses in vivo antibody response

Exposure to an intense acute stressor immediately following immunization leads to a reduction in anti-KLH IgM, IgG, and IgG2a, but not IgG1. Stress also depletes splenic norepinephrine (NE) content. Immunization during pharmacological (alpha-methyl-p-tyrosine) or stress-induced splenic NE depletion results in antibody suppression similar to that found in rats immunized prior to stressor exposure. Prevention of splenic NE depletion during stress by tyrosine, but not pharmacological elevation (mirtazapine) of NE, resulted in normal antibody responses. These data support the hypothesis that splenic NE depletion is necessary and sufficient for stress-induced suppression of antibody to a T-cell dependent antigen.

Regulation of brain IL-1 production following peripheral E. coli challenge: A role for the nucleus tractus solitarius and locus coeruleus

The relationship between stress and post-surgical WBC count among women undergoing total abdominal hysterectomy with bilateral salpingo oophorectomy (TAH-BSO) for suspected endometrial cancer Sally E. Jensen , Deidre B. Pereira , Stacy M. Dodd , Melissa Hosonitz , Daylene Ripley , Linda Morgan b a Department of Clinical and Health Psychology, University of Florida, USA b Department of Obstetrics and Gynecology, University of Florida, USA

Ovariectomy alters the induction of heat shock protein 72 in some stress-responsive tissues

In addition to its common use as a spice, the medical uses of garlic (Allium sativum) have been known for centuries. More recently, the anti-bacterial and anti-fungal activity of garlic has been verified and the anti-artherosclerosis, anti-carcinogenesis, and hypolipidemic activities for garlic and several of its constituents have been demonstrated. In addition, anti-oxidant, anti-inflammatory, anti-ageing, and anti-stress effects have been reported for a well-characterized aged garlic extract (AGE, Kyolic ). We have examined further the possible anti-stress effects of AGE. We first tested the effects of 15 min cold water immersion (15 C) on LPS (10 lg i.v.) induced plasma and splenic inflammatory cytokine production, as well as corticosterone and catecholamine levels. Blood and spleen were harvested 90 min following LPS injection. Relative to controls, cold water immersion produced a significant decrease in plasma levels of TNF-a and IL-6 and splenic levels of TNF-a, IL-1b, and IL-6. Also, cold water immersion produced a significant decrease in plasma corticosterone levels, but increased plasma norepinephrine and epinephrine levels. We next tested the effects of orally administering AGE (10 ml/ kg) daily via gavage for 5 days prior to 15 min cold water immersion challenge and i.v. LPS injection. Relative to rats pretreated with vehicle, the AGE treated animals showed an attenuation in the immunosuppressive effects of cold water immersion on plasma and spleen levels of IL-6, and splenic levels of IL-1b. The stress-induced suppression of TNF-a levels were not altered by AGE. However, AGE treatment blocked the stress-induced changes in plasma levels of corticosterone, norepinephrine and epinephrine. Thus, pretreatment with AGE was able to partially reverse the effects of cold water stress on LPS-induced cytokine production, and completely block the stress-LPS induced changes in plasma corticosterone and catecholamine levels. These results indicate that AGE can counteract some of the immunomodulatory effects of stress which may be mediated via AGE-induced changes in the neuroendocrine and autonomic nervous systems.

102 The female intracellular Hsp72 stress response

ther the immunoregulatory effects of counter-irritation, we have tested the effects of turpentine injections into themuscle (IM), skin (ID)or plantar foot (PF) of the hindlimbof rats on endotoxin (LPS) induced plasma and splenic cytokines and catecholamine levels and plasma corticosterone. One hour following saline or turpentine injections (50–100 ll), rats were injected IV with LPS (10 lg) and then sacrificed one hour later. Relative to saline injections, both IM and PF injections of turpentine produced a significant decrease in plasma and splenic levels of TNF protein whereas IL-1 and IL-6 levels were unaltered by pretreatment with turpentine. In addition, PF injections of turpentine produced a significant decrease of corticosterone levels. In contrast, the effects of ID injections of turpentine were limited to a significant increase in splenic TNF levels and a tendency to increase plasma TNF levels. To examine the role of the sympathetic nervous system, we pretreated rats IP with the peripheral beta-adrenergic blocking agent Nadolol (2 mg/kg) 30 min prior to an IM injection of saline or turpentine. LPS was injected 1 h post-turpentine/saline and the rats were sacrificed one hour later. Pretreatment with Nadolol blocked the suppression in splenic and plasma levels of TNF produced by IM turpentine, consistent with the sympathetic mediation of the immunoregulatory effects of counter-irritation. Our data indicate further that the immunomodulatory effects of ID turpentine may be quite distinct from that observed with IM and PF injections. Supported by the NIMH of the United States (MH 43778).