Influence of bromocriptine administration to mothers on the development of pup thymocyte and splenocyte subsets and on mitogen-induced proliferation in the mouse

Abstract

The influence of prolactin (PRL) on the development of the immune system in the mouse was studied by injecting mothers with bromocriptine (CB-154) to produce hypoprolactinemic milk. Alterations in pup thymocyte and splenocyte cell subsets were observed to graded doses of CB-154 administered to mothers. There was an increase in the relative percentages of neonate thymic CD4 and CD8 cells at 5 days of age when mothers were injected with 100 μg of CB-154 2 x daily from day 1 to 5 of lactation, however, there was no alteration in absolute thymic subset cell numbers. The relative percentage of pup spleen CD4, CD8 and B cells were increased when mothers were administered 50 or 100 μg of CB-154 and the 50 μg dose resulted in a significant increase in the absolute number of CD4 cells while the 100 μg dose induced a significant decrease in the three splenic cell subsets examined. Graded doses of CB-154 administered to mothers resulted in decreases in the PRL concentration of stomach milk as measured by the Nb2 cell proliferation assay. The serum PRL level of the pups, however, was not altered by any dose of CB-154 injected to the mothers. The administration of PRL to pups nursing mothers given the 100 μg dose of CB-154 did not alter the pup thymocyte and splenocyte subset population from that of litter-mate controls. The administration of mouse PRL and mouse growth hormone antisera to pups nursing saline-injected mothers did not alter thymocyte and splenocyte subsets from that of saline-injected litter mate controls. The proliferation of neonatal thymocytes by Con-A stimulation was not altered by CB-154 injection to mothers and PRL administration to pups. However, since the percentage of thymic CD4 and CD8 cells in the thymus was increased 2 to 3 fold, the apparent lack of effect was in fact a decrease in the responsiveness of the thymocytes. Con-A stimulation of neonatal splenocytes resulted in a significant increase in proliferation for mothers administered CB-154 in keeping with the increase relative percentage of CD4 and CD8 cells observed. Prolactin administration to the pups did not alter the response. LPS stimulation of neonatal splenocytes increased the proliferation of B cells taken from pup nursing mothers administered CB-154 and PRL administration appeared to partially block this proliferation. The data suggest that the changes observed in thymocyte and splenocyte subsets of pups nursing mothers receiving CB-154 was not due to the hypoprolactinemic milk but may be due to other factors such as undernutrition. A growing body of evidence in the adult has implicated prolactin (PRL) in the regulation of the immune system (1). The involvement of PRL in the development of the immune system has not been extensively studied. In the neonatal mouse the secretion of pituitary PRL is not detected until after the eighth day of life (2) although a number of investigators have detected PRL in the serum of rat pups (3,4) and mouse pups (5) by radioimmunoassay prior to this time. This apparent contradiction was resolve when it was determined that milk, from a wide number of species, contained high levels of PRL (6–9) and that it was biologically active (10,11). In addition, it was also reported that the PRL in milk was transferred to the circulation of the neonatal rat (12) and that pup serum PRL was biologically active (13). Grosvenor and associates (14) demonstrated that the administration of low doses of bromocriptine, a drug that specifically suppresses pituitary prolactin, to lactating mother rats would decrease the level of PRL in the milk. They also observed that when the pups reach adulthood they had hyperprolactinemia and a disruption in tuberoinfundibular dopamine neural activity (15). Thus, a decrease in milk PRL exposure during early neonatal life resulted in the disruption of the physiologic regulation of PRL when the pups reached adulthood. The involvement of PRL in the development of the immune system during the neonatal period has been examined in rats and mice (16, 17). The purpose of this study was to determine the effect of PRL on the neonatal development of the immune system in the mouse. To accomplish this bromocriptine was administered to lactating mothers and alterations in thymocyte and splenocyte subset populations were examined as well as their in vitro proliferation to mitogens. In addition we also examined the administration of anti-mouse PRL and anti-mouse growth hormone (GH) sera as well as replacement injections of PRL to pups nursing mothers who received bromocriptine.