Mechanism of depressed immunity in chronic renal failure: effect of cyclophosphamide pretreatment on delayed-type hypersensitivity skin reaction.

An imbalance in immunoregulatory mechanisms resulting in a relative increase in suppressor cell activity has been implicated in the development of the immunological deficit observed in chronic uremia. The present study was designed to assess whether cyclophosphamide pretreatment would preferentially enhance immune responses of chronically uremic animals. Delayed-type hypersensitivity (DTH) skin responses to oxazolone were found significantly decreased in chronically uremic mice as compared with sham-operated and normal controls. The administration of a single high dose (250 mg/kg) of cyclophosphamide 3 days prior to skin sensitization with oxazolone resulted in enhancement of DTH responses in all mice groups. Maximal increases in DTH responses following cyclophosphamide treatment was 61.6% in chronically uremic mice, and 100.5 and 86.2% in sham-operated and normal controls, respectively. The levels of active metabolites of cyclophosphamide, as estimated indirectly by the degree of myelosuppression achieved, were comparable across the 3 mice groups. These results thus fail to provide evidence for excessive numbers of cyclophosphamide-sensitive suppressor cells in chronic experimental uremia.