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

Shock. 2000 Nov;14(5):561-4. doi: 10.1097/00024382-200014050-00011.


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.

MeSH terms

  • Animals
  • Corticosterone / blood
  • Endotoxemia / blood
  • Endotoxemia / physiopathology*
  • Endotoxins / toxicity*
  • Interferon-gamma / biosynthesis*
  • Interferon-gamma / blood
  • Lipopolysaccharides / toxicity
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Stress, Physiological / blood
  • Stress, Physiological / physiopathology*
  • Surgical Procedures, Operative*
  • Tumor Necrosis Factor-alpha / biosynthesis*


  • Endotoxins
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • endotoxin, Escherichia coli
  • Interferon-gamma
  • Corticosterone