ENDOTOXIN AND TUMOR-NECROSIS-FACTOR DO NOT CAUSE MORTALITY FROM CECALLIGATION AND PUNCTURE

Macrophage tumour necrosis factor-alpha (TNF-alpha) production is thou ght to represent an important pathogenic mechanism by which Gram-negat ive sepsis is mediated. We compared the effects of caecal ligation and puncture (CLP) on endotoxin-sensitive (C3H/HeSnJ) and endotoxin-resis tant (C3H/HeJ) mice. Mortality after CLP for C3H/HeSnJ mice compared w ith C3H/HeJ mice was not significantly different (32% and 55%, respect ively). When survivors were injected with lipopolysaccharide intraperi toneally on the 7th day after CLP, the mortality rate was 82% for C3H/ HeSnJ mice versus 0% for C3H/HeJ mice (P < 0.0001). Serum endotoxin le vels at 24 h after CLP were only slightly elevated. Serum TNF levels a nd peritoneal macrophage TNF production were undetectable in C3H/HeJ m ice and were only slightly elevated in C3H/HeSnJ mice by 24 h after CL P. Peritoneal macrophage mRNA levels for TNF-alpha, IL-1 beta, and I-A alpha displayed a similar pattern in the two strains of mice, with a 2- to 3-fold increase in TNF-alpha and IL-1 beta mRNA levels by 24 h a nd a sharp decrease in I-A alpha mRNA by 24 h. The cause of mortality in mice that undergo CLP cannot be attributed to overwhelming endotoxe mia and/or TNF production.