Induction of suppressor cell activity in vivo and suppression of lymphoproliferative responses in vitro by SK&F 105685 in the dog

Abstract

SK&F 105685 (N,N-dimethyl-8,8-dipropyl-2-azaspiro[4.5]decane-2-propanamine dihydrochloride) is a novel azaspirane with beneficial activity in rat models of adjuvant-induced arthritis and experimental autoimmune encephalomyelitis as well as in the murine lupus model. The mechanism of action in these models appears to be the induction of non-specific suppressor cell activity which is measured by the ability of cells from treated animals to partially inhibit the proliferative response of lymphocytes from control animals to concanavalin A (ConA) in a co-culture assay. In this study we have shown that oral administration of 0.1–3 mg/kg/day of SK&F 105685 to purebred beagle dogs induced suppressor cell activity in the spleen and bone marrow but not in the peripheral blood. In vitro, SK&F 105685 partially suppressed the proliferative response of dog splenocytes to the mitogens phytohemagglutinin (PHA), ConA and, to a lesser extent, pokeweed mitogen (PWM). Peripheral blood lymphocytes (PBLs) differed from spleen cells in their susceptibility to suppression by SK&F 105685. While the PWM and ConA responses of PBLs and spleen cells showed similar levels of inhibition, the PHA response; of PBLs, in marked contrast to spleen cells, was resistant to suppression by the compound. Our results show that the immunoregulatory effects of SK&F 105 685 are not limited to rodents and that suppressor cell activity in dogs is induced quickly and by relatively low doses of the compound.