Nonstressed rat model of acute endotoxemia that unmasks the endotoxin-induced TNF-alpha response

Previous investigators have demonstrated that the tumor necrosis factor-alp ha (TNF-alpha) response to endotoxin is inhibited by exogenous corticostero ne or catecholamines both in vitro and in vivo, whereas others have reporte d that surgical and nonsurgical stress increase the endogenous concentratio ns of these stress-induced hormones. We hypothesized that elevated endogeno us stress hormones resultant from experimental protocols attenuated the end otoxin-induced TNF-alpha response. We used a chronically catheterized rat m odel to demonstrate that the endotoxin-induced TNF-alpha response is 10- to 50-fold greater in nonstressed (NS) rats compared with either surgical-str essed (SS, laparotomy) or nonsurgical-stressed (NSS, tail vein injection) m odels. Compared with the NS group, the SS and NSS groups demonstrated signi ficantly lower mean peak TNF-alpha responses at 2 mg/kg and 6 mu g/kg endot oxin [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 mu g/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 g roup 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-alpha response. Subsequent studies of endotoxic shock should control for the effects of protocol-induced stress and should measu re and report baseline concentrations of corticosterone and catecholamines.