The effect of surgical stress on the endotoxin-induced interferon-gamma response

Most animal studies of cytokine release during sepsis or endotoxemia have u sed models in which studies are performed during or immediately after surgi cal stress. In a previous study, we showed that surgical stress as measured by elevated endogenous corticosterone concentrations attenuated the endoto xin-induced tumor necrosis factor alpha (TNF alpha) response. To determine whether surgical stress attenuates the endotoxin-induced interferon-gamma ( IFN-gamma) response, chronically catheterized male Sprague-Dawley rats were treated with endotoxin 10 mug/kg immediately after surgery for catheter pl acement (surgical stress group, SS group) or at least 4 days postoperative (nonstressed group, NS group). We found that peak endotoxin-induced IFN-gam ma responses were similar in the SS and NS groups (2094 +/- 315 pg/mL vs. 1 863 +/- 307 pg/mL). Baseline corticosterone concentrations were significant ly elevated in the SS group compared to the NS group (273.8 +/- 15.2 ng/mL vs. 30.0 +/- 8.5 ng/mL, P < 0.001). Peak TNFa concentrations were significa ntly reduced in the SS group compared to the NS group (5.2 +/- 1.9 ng/mL vs . 69.9 +/- 10.3 ng/mL, P = 0.0002). While peak serum TNF<alpha> concentrati ons were inversely related to baseline corticosterone concentrations, there was no correlation between peak IFN-gamma concentrations and baseline cort icosterone concentrations or between TNF alpha and IFN-gamma concentrations . We conclude that surgical stress associated with elevated concentrations of endogenous corticosterone does not attenuate the endotoxin-induced IFN-g amma response despite an attenuation of the endotoxin-induced TNF alpha res ponse. Because the effect of stress on different cytokines is varied, studi es of sepsis and endotoxemia must account for the effects of experimentally -induced stress on cytokine responses.