Monitoring of immunosuppression in beagles

Abstract

The effects of immunosuppressive drugs were measured after 2, 5, and 9 months of treatment during canine bronchial carcinogenesis experiments. Antibody titers to bovine red blood cells, rat blood cells, and chicken γ-globulin were determined, and skin allografts were used to test levels of immunity. Delayed cutaneous hypersensitivity responses to rabies vaccine, combination distemper-hepatitis-leptospirosis vaccine, and 3,5-dinitrochlorobenzene (DNCB) were evaluated. Absolute lymphocyte counts were the most sensitive dose-related nonspecific indicators of the level of immunosuppression. High dose immunosuppression (HIS) with azathioprine, 2.5 mg/kg/day, and methylprednisolone, 1.0 mg/kg/day, depressed antibody responses within 2 months ( P < 0.01). HIS also prolonged skin allograft rejection from 6.5 ± 0.9 to 14.1 ± 1.1 days ( P < 0.01), and it suppressed cutaneous responses to distemper vaccine and DNCB ( P < 0.01). Most beagles could not tolerate HIS chronically under the conditions of our experiments. Low dose immunosuppression (LIS) at one-half the HIS level was well tolerated. LIS prolonged skin allograft rejection to 10.8 ± 1.0 days ( P < 0.01), and it also suppressed cutaneous hypersensitivity ( P < 0.01). LIS inhibited antibody responses after 9 months of treatment ( P < 0.01), but not after 2 months of therapy. All of the skin tests provided evidence of immunosuppression but none did so consistently. Distemper vaccine gave the clearest responses. We conclude that an approach which quantitates immunosuppression in dogs has broad practical applicability to canine transplantation and carcinogenesis research.