Postburn immunosuppression in an animal model. IV. Improved resistance to septic challenge with immunomodulating drugs

We have previously demonstrated that certain pharmacologic agents administered to burned mice will restore cell-mediated immunity, as evidenced by measurement of delayed hypersensitivity responses and determination of splenic helper/suppressor lymphocyte ratios. These drugs are systemic cimetidine, ibuprofen, cyclophosphamide, and topical cerium nitrate. In the studies reported here we performed cecal ligation and puncture (CLP) in burned mice as a measure of resistance to infectious challenge. Survival after CLP with a 23-gauge needle used for puncture was markedly decreased when performed on the tenth postburn day (normal 63.7%, 10 days postburn 20.0%; p < 0.001), but survival was not decreased when CLP was performed on the fifth (60.0%; p not significant) or twenty-first postburn day (65.3%; p not significant). Animals were then treated with the four agents in carefully defined dosage regimens, and survival was again determined on the tenth postburn day. Survival figures with p values compared to burned, untreated animals: burn plus cimetidine 62.2%, p < 0.0005; burn plus: ibuprofen 64.7% p < 0.0003; burn plus cyclophosphamide 68.2%, p < 0.0001; burn plus cerium nitrate 54.1%, p < 0.004. Specific pharmacologic therapy in burned mice in dosage regimens that have been shown to improve cell-mediated immunity is also able to significantly improve resistance to subsequent infectious challenge.