Age-dependent effect of pituitary transplants on immune responses in rat spleen: modulatory effect of cyclosporine.

Abstract

Male rats were grafted an anterior pituitary within breast muscles on day 5 or under the kidney capsule on day 30 or 60 of life. On the 70th day of life (rats operated on the 5th or 30th day) or on the 100th day of life (rats operated on the 60th day), rats were injected subcutaneously with Freund's complete adjuvant, being killed 2 days later. Rats that had received a pituitary graft on the 30th day showed a greater degree of hyper-prolactinemia than rats grafted on the 5th or 60th day. Analyzed as main factors in a factorial analysis of variance (ANOVA), pituitary transplants augmented splenic natural killer (NK) activity and lipopolysaccharide (LPS)- and concanavalin A (Con A)-induced cell proliferation, and decreased splenic cell number. As indicated by significant interactions between treatment and age of transplantation in a factorial ANOVA, splenic NK activity augmented in rats grafted on the 30th day of life, while LPS and Con A splenic cell proliferation augmented in rats grafted neonatally. Spleen cellularity decreased after pituitary transplants in 30- and 60-day-old rats. In a second study, the effect of cyclosporine on spleen immune responses was tested by administering cyclosporine (5 mg/kg) or vehicle to rats grafted as in experiment 1 for 5 days before sacrifice. Cyclosporine decreased splenic NK activity and LPS- and Con A-induced cell proliferation regardless of the presence of a pituitary graft. In rats grafted on the 30th day of life, cyclosporine reversed the effect of pituitary grafts on splenic NK activity, and ectopic pituitary augmenting NK activity in vehicle-treated rats while decreasing it in cyclosporine-injected rats. Cyclosporine reversed the inhibitory effect of pituitary transplants on spleen cell number. The high circulating prolactin levels found in rats with pituitary grafts were decreased by cyclosporine administration. The results are compatible with age-dependent promoting and inhibitory effects of hyperprolactinemia on the immune responses of the spleen, which were antagonized by cyclosporine immunosuppression.