Previous investigators have demonstrated that the tumor necrosis factor- (TNF-) response to endotoxin is inhibited by exogenous corticosterone or catecholamines both in vitro and in vivo, whereas others have reported that surgical and nonsurgical stress increase the endogenous concentrations of these stress-induced hormones. We hypothesized that elevated endogenous stress hormones resultant from experimental protocols attenuated the endotoxin-induced TNF- response. We used a chronically catheterized rat model to demonstrate that the endotoxin-induced TNF- response is 10- to 50-fold greater in nonstressed (NS) rats compared with either surgical-stressed (SS, laparotomy) or nonsurgical-stressed (NSS, tail vein injection) models. Compared with the NS group, the SS and NSS groups demonstrated significantly lower mean peak TNF- responses at 2 mg/kg and 6 µg/kg endotoxin [NS 111.8 ± 6.5 ng/ml and 64.3 ± 5.9 ng/ml, respectively, vs. SS 3.9 ± 1.1 ng/ml (P < 0.01) and 1.3 ± 0.5 ng/ml (P < 0.01) or NSS 5.2 ± 3.2 ng/ml (P < 0.01) at 6 µg/kg]. Similarly, baseline concentrations of corticosterone and catecholamines were significantly lower in the NSS group [84.5 ± 16.5 ng/ml and 199.8 ± 26.2 pg/ml, respectively, vs. SS group 257.2 ± 35.7 ng/ml (P < 0.01) and 467.5 ± 52.2 pg/ml (P < 0.01) or NS group 168.6 ± 14.4 ng/ml (P < 0.01) and 1,109.9 ± 140.7 pg/ml (P < 0.01)]. These findings suggest that the surgical and nonsurgical stress inherent in experimental protocols increases baseline stress hormones, masking the endotoxin-induced TNF- response. Subsequent studies of endotoxic shock should control for the effects of protocol-induced stress and should measure and report baseline concentrations of corticosterone and catecholamines.

catecholamines; corticosterone; stress; endogenous

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