Interferon gamma and tumor necrosis factor alpha. Use in gram-negative infection after shock

M. A. Malangoni, D. H. Livingston, G. Sonnenfeld and H. C. Polk Jr
Department of Surgery, University of Louisville, KY 40292.

Shock increases the propensity to develop infection after injury or operation. This study evaluated the effect of cefoxitin, interferon gamma (INF-gamma), and tumor necrosis factor alpha (TNF-alpha) on the development of a polymicrobial soft-tissue infection. After sham operation or hemorrhagic shock and resuscitation, Sprague-Dawley rats were inoculated with 1 x 10(8) Escherichia coli and 1 x 10(9) Bacteroides fragilis in a 5% fecal suspension. Animals received either no treatment, cefoxitin, recombinant rat INF-gamma, recombinant human TNF-alpha, or cefoxitin/cytokine combinations. Cefoxitin reduced abscess size by 57% in animals without shock but only by 26% after shock. Although neither INF-gamma nor TNF-alpha alone had a salutary effect when given with cefoxitin in animals after shock, INF-gamma and TNF-alpha reduced abscess size by 50% and 55%, respectively. These results suggest that INF-gamma and TNF-alpha may be useful to reduce the severity of mixed gram-negative infections after shock with bacterial contamination.