An evaluation of cyclophosphamide as an immunomodulator in multiple septic animal models

Cyclophosphamide has shown promise as an immunomodulator in early animal trials involving mice and guinea pigs. To test the effectiveness of this agent in a rat model, 268 adult Lewis rats were subjected to a 30% total body surface area burn and were challenged with Pseudomonas aeruginosa 1244 administered intraperitoneally on postburn day 1 or 4, or painted on the burn wounds on postburn day 1. The animals were then followed up to determine mean survival times and survival rate percentages. Cyclophosphamide was administered to the animals on postburn days 0, 2, and 4 at a dose of either 0.5, 1.0, 5.0, or 15.0 mg/kg. A final group received saline. None of the doses significantly prolonged survival in any of the septic models, and the 15 mg/kg dose significantly shortened it in all three models. Thus, the beneficial immunomodulatory effects previously seen in mouse and guinea pig models were not seen in the rat model. Further animal investigations would appear to be indicated before human studies are undertaken.