Differential expression of interleukin-1 and tumor necrosis factor in murine septic shock models.

Murine shock models have employed bolus endotoxin as well as cecal ligation and puncture (CLP) in an attempt to understand the pathophysiologic changes associated with human septic shock. Injection of endotoxin results in a rapid but transient rise in tumor necrosis factor (TNF), with maximal levels between 1 and 2 hr followed by an increase in serum interleukin-1 (IL-1) by 3 hr which remains elevated at 24 hr. CLP animals in contrast do not demonstrate an elevation in serum TNF, and the increase in IL-1 is less significant relative to the endotoxin model. Whereas both models demonstrate comparable increases in serum amyloid A protein and result in host death between 24 and 48 hr, these models respond differently to therapeutic modalities. Steroids and an anti-TNF monoclonal antibody administered prophylactically are effective at preventing death in the endotoxin model and yet had no beneficial effect in antibiotic-treated CLP animals. Experiments with adrenalectomized mice suggest that the absence of serum TNF in the CLP model is in part due to the modulatory effects of endogenous corticosteroids.