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.