Experimental autoimmune tubulointerstitial nephritis in guinea-pigs: effects on renal lesions of cyclophosphamide administered before and after tubular basement membrane immunization

摘要

To evaluate the role of immune cells, including suppressor cells, in the tubular basement membrane model (TBM) of autoimmune tubulointerstitial nephritis (TIN) in guinea-pigs, a single high dose of cyclophosphamide (200 mg/kg body weight) was administered intraperitoneally 72 hr before or 72 hr after TBM/FCA (Freund's complete adjuvant, 500 μg/ml) immunization. Animals were divided into control, Group I (TBM immunized, no cyclophosphamide), Group II (cyclophosphamide 72 hr before TBM immunization) and Group III (TBM immunization, 72 hr later cyclophosphamide). Renal lesions in Groups II and III were either mild or absent and no linear deposits of IgG on tubular basement membrane were observed; in contrast Group I animals had renal interstitial infiltrate of mononuclear and giant cells and linear IgG deposits on tubular basement membrane.Since cyclophosphamide pretreatment at high dosages can remove susceptible suppressor cells and their precursors and enhance some forms of delayed hypersensitivity, the lack of enhanced renal lesions with 72 hr cyclophosphamide pretreatment suggests that subsets of antigen-specific suppressor cells sensitive to cyclophosphamide are not significant in the pathogenesis of the renal lesions of TIN; whereas, in animals given cyclophosphamide after immunization, absence of lesions reflects effect of cyclophosphamide on rapidly dividing cells. The findings also support the central role of anti-TBM autoantibody in the pathogenesis of this model of tubulointerstitial nephritis.