The effect of surgical stress on the endotoxin-induced interferon-gamma response.
Most animal studies of cytokine release during sepsis or endotoxemia have used models in which studies are performed during or immediately after surgical stress. In a previous study, we showed that surgical stress as measured by elevated endogenous corticosterone concentrations attenuated the endotoxin-induced tumor necrosis factor alpha (TNFalpha) 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 microg/kg immediately after surgery for catheter placement (surgical stress group, SS group) or at least 4 days postoperative (nonstressed group, NS group). We found that peak endotoxin-induced IFN-gamma responses were similar in the SS and NS groups (2094 +/- 315 pg/mL vs. 1863 +/- 307 pg/mL). Baseline corticosterone concentrations were significantly 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 TNFalpha concentrations were significantly 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 TNFalpha concentrations were inversely related to baseline corticosterone concentrations, there was no correlation between peak IFN-gamma concentrations and baseline corticosterone concentrations or between TNFalpha and IFN-gamma concentrations. We conclude that surgical stress associated with elevated concentrations of endogenous corticosterone does not attenuate the endotoxin-induced IFN-gamma response despite an attenuation of the endotoxin-induced TNFalpha response. Because the effect of stress on different cytokines is varied, studies of sepsis and endotoxemia must account for the effects of experimentally-induced stress on cytokine responses.
Esguerra LEO
Department of Pediatrics, Cook County Hospital, Chicago, IL 60612, USA.
Beno DWA
Deriy
L
L
Kimura
R E
RE
Uhing
M R
MR
D000818:Animals; D003345:Corticosterone / Q000097:blood; D019446:Endotoxemia / Q000097:blood / Q000503:physiopathology*; D004731:Endotoxins / Q000633:toxicity*; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000097:blood; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000097:blood / Q000503:physiopathology*; D013514:Surgical Procedures, Operative; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D004731:Endotoxins; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C044101:endotoxin, Escherichia coli; D007371:Interferon-gamma; D003345:Corticosterone