Hemorrhagic shock increases the susceptibility to infection in both clinical and laboratory settings. Hemorrhagic shock also is associated with a decreased production of interferon-γ (IFN-γ), a potent modulator of immune function. We investigated the effect of IFN-γ both alone and in addition to antibiotic prophylaxis upon infection following hemorrhagic shock. Sprague-Dawley rats were bled to a mean arterial pressure of 45 mm Hg for 45 min and then were resuscitated with shed blood and normal saline. Abscess formation was induced 1 hr later by subcutaneous injection of 1 × 108 Staphylococcus aureus. Four treatments were investigated: (1) control; (2) recombinant rat IFN-γ, 7500 units, 30 min after inoculation and daily for 3 days; (3) cefamandole (CEF) nafate, 30 mg/kg, 30 min before and 4 hr after inoculation; and (4) IFN-γ + CEF as in (2) and (3). Abscess size, weight, and quantitative bacterial counts were measured 7 days after inoculation. Hemorrhagic shock increased mean abscess size from 11.7 ± 2.8 to 14.1 ± 1.9 mm (P < 0.05), in untreated rats. IFN-γ alone resulted in minor changes in abscess formation in both shocked and unshocked animals. Shock rendered CEF ineffective in reducing abscess size. IFN-γ + CEF significantly reduced abscess size (14.1 ± 1.9 to 8.1 ± 1.8 mm) and weight (771 ± 214 to 252 ± 132 mg) and decreased bacterial count after shock to 12% of control (all P < 0.05). These data demonstrate that hemorrhagic shock impairs antibiotic efficacy; however, the addition of IFN-γ restores the ability of host defenses to combat bacterial infection.
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