Immune enhancement by tumor necrosis factor-alpha improves antibiotic efficacy after hemorrhagic shock

Immunomodulation with cytokines produced by recombinant DNA technology may be useful in combatting the increased susceptibility to infection seen after shock and trauma. We investigated the effect of tumor necrosis factor (TNF) alone and in combination with an antibiotic in a model of infection after shock. Interactions of TNF with another cytokine, interferon-gamma (IFN-gamma), were also examined. Sprague-Dawley rats were bled to maintain blood pressure at 45 mm Hg for 45 minutes and then resuscitated with shed blood and saline. Animals were inoculated with 10s 5. aureus subcutaneously and placed into one of seven treatment groups: 1) control; 2) CEF-cefazolin, 30 mg/kg IP, 30 minutes before and 4 hours after inoculation; 3) IFN-recombinant rat IFN-gamma, 7,500 U SQ, 30 minutes after inoculation and daily for 3 days; 4) TNF-recombinant human TNF, 7,500 U SQ, 30 minutes after inoculation and daily for 3 days; 5) CEF+IFN as in 2 and 3; 6) CEF+TNF as in 2 and 4; 7) CEF+IFN+TNF as in 2, 3, and 4. Animals were sacrificed on day 7 and abscess number, diameter, and weight were measured. CEF reduced abscess diameter and weight following hemorrhagic shock, but did not affect abscess number. IFN-gamma and TNF alone did not reduce infection. The combination of either IFN-gamma or TNF with CEF significantly decreased infection following shock compared to control or CEF alone. CEF+TNF decreased abscess number compared to CEF+IFN (14/20 vs. 7/20;p < 0.05) but did not alter abscess diameter. No additive effect of IFN-gamma and TNF with CEF was evident. These data demonstrate that the addition of TNF to CEF decreases the incidence of S. aureus infection after hemorrhagic shock.