Endocrine-immune interaction: Alterations in immune function resulting from neonatal treatment with a GnRH antagonist and seasonality in male primates

PROBLEM: The effect of neonatal gonadotropin releasing hormone (GnRH) antag onist (Ant) treatment and seasonality on immune system development and func tion was investigated in male primates. METHOD OF STUDY: Neonatal male rhesus monkeys and marmosets were treated wi th Ant, and its effect on immune system morphology, circulating lymphocyte subsets, and cell- and humorally-mediated immune responses was assessed dur ing development. In adult rhesus monkeys, we correlated seasonal changes in immune function with circannual fluctuations in immunoactive hormones. RESULTS: In neonatal marmosets, Ant reduced the number of B cells and T cel ls in the thymic medulla and T cells in the periarterial lymphatic sheaths (PALS) of the spleen. Ant also altered the development of, but did not perm anently impair, the proliferative index (PI) of blood lymphocytes to mitoge ns. In vitro treatment of control lymphocytes with GnRH analogues altered t heir response to these proliferative agents. In neonatal rhesus monkeys, An t treatment increased the frequency of clinical problems, lowered circulati ng levels of lymphocytes, total T cells, CD8 + T cells and B cells. and alt ered the PI of lymphocytes to mitogens. As adults, the cell- and humorally- mediated immune responses remained impaired. We also documented seasonal fl uctuations in the prevalence of diseases, circulating immune cells and immu ne function in rhesus monkeys. The number of cases of campylobacteriosis an d shigellosis was lowest in the winter and highest in the spring. Circulati ng numbers of white blood cells (WBC) and neutrophils and the PI of lymphoc ytes to mitogens were higher in the winter than in the summer. Natural kill er cell activity also varied with season. Cortisol and leptin secretion exh ibited circannual rhythms, rising in concert with decreasing photoperiod an d increasing testicular activity in the fail. Conversely, prolactin levels declined with decreasing photoperiod and then rose in the spring. CONCLUSION: Neonatal exposure of male primates to Ant appears to alter earl y postnatal programming of immune function. In the rhesus monkey, immune fu nction shows seasonal fluctuations that may be driven by circannual changes in the secretion of immunoactive hormones.