Pretreatment with Recombinant Murine Tumor Necrosis Factor Alpha/Cachectin and Murine Interleukin 1 Alpha Protects Mice from Lethal Bacterial Infection.

摘要

Tumor necrosis factor alpha/cachectin (TNF/C) is a well -characterized peptide that may, through its diverse effects on cells, mediate many normal host functions, including tissue remodeling and the mobilization of energy reserves required by the infected host. Tumor necrosis factor/cachectin (TNF/C) is the principal mediator of bacterial endotoxin-induced shock and death. We found that the C3H/HeJ mouse, which is less able able to produce TNF/C in response to endotoxin, has a thousand-fold greater susceptibility to lethal infection with E. coli than the TNF-responsive congenic mouse, CeH/HeN. This surprising finding suggested that this lethal peptide may also be involved in host protection. To test this hypothesis we pre-treated the C3H/HeJ mouse with a combination of recombinant murine TNF/C alpha and interleukin-1 alpha. This combination protected these mice against an intraperitoneal bacterial challenge of more than 20 LD 50s (nearly 200 CFU) and which grew to a level of >107 CFU/ml of blood and per gram liver in untreated mice. This suggests a significant role for these cytokines in host defenses against invasive infections that require bacterial replication within the host. These protective mechanisms may not be important for less virulent organisms. These findings may have important implications for the proposed use of anti-TNF/C agents in the treatment of septic shock. Reprints. (aw)