Pathogenesis of Pseudomonas aeruginosa pneumonia during immunosuppression

Abstract

A guinea pig model of immunosuppression was utilized to study the effects of immunosuppressive chemotherapy on lung response to challenge with Pseudomonas aeruginosa. Study groups included normal guinea pigs, as well as guinea pigs that received a one-week course of cortisone acetate (CA, 100 mg/kg per day) plus 15 mg of cyclophosphamide (CTX)/kg per day (CA + LoCTX group) or 30 mg of cyclophosphamide/kg per day (CA + HiCTX group). Separate groups received CA or HiCTX alone. Intratracheal instillation of P. aeruginosa resulted in bilateral hemorrhagic pneumonia in both normal and immunosuppressed animals. Survival was 100% for normal animals and for those given CA alone, 67% in the CA + LoCTX and the HiCTX groups, and 0 in the CA + HiCTX group. Increased mortality correlated with a diminished polymorphonuclear leukocyte inflammatory response in infected lung tissues and also with the addition of CA to CTX. Clearance of viable P. aeruginosa from lung tissue was significantly reduced in animals receiving the combination CA + HiCTX. Thus, decreased lung inflammation and the addition of CA appeared to be important determinants for fatal pseudomonas pneumonia.