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 less than 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 less than 0.0005; burn plus: ibuprofen 64.7% p less than 0.0003; burn plus cyclophosphamide 68.2%, p less than 0.0001; burn plus cerium nitrate 54.1%, p less than 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.
D000818:Animals; D000891:Anti-Infective Agents, Local / Q000627:therapeutic use*; D002056:Burns / Q000150:complications / Q000276:immunology*; D002563:Cerium / Q000627:therapeutic use*; D002927:Cimetidine / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007052:Ibuprofen / Q000627:therapeutic use*; D007108:Immune Tolerance / Q000187:drug effects*; D007111:Immunity, Cellular / Q000187:drug effects; D017053:Infection Control; D007239:Infections / Q000276:immunology; D051379:Mice; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000891:Anti-Infective Agents, Local; C032786:cerium nitrate; D002563:Cerium; D002927:Cimetidine; D003520:Cyclophosphamide; D007052:Ibuprofen