Endocrine-immune interaction: alteractions 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) antagonist (Ant) treatment and seasonality on immune system development and function was investigated in male primates. METHOD OF STUDY: Neonatal male rhesus monkeys and marmosets were treated with Ant, and its effect on immune system morphology, circulating lymphocyte subsets, and cell- and humorally-mediated immune responses was assessed during 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 cells 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 permanently impair, the proliferative index (PI) of blood lymphocytes to mitogens. In vitro treatment of control lymphocytes with GnRH analogues altered their response to these proliferative agents. In neonatal rhesus monkeys, Ant treatment increased the frequency of clinical problems, lowered circulating levels of lymphocytes, total T cells, CD8+ T cells and B cells, and altered the PI of lymphocytes to mitogens. As adults, the cell- and humorally-mediated immune responses remained impaired. We also documented seasonal fluctuations in the prevalence of diseases, circulating immune cells and immune function in rhesus monkeys. The number of cases of campylobacteriosis and shigellosis was lowest in the winter and highest in the spring. Circulating numbers of white blood cells (WBC) and neutrophils and the PI of lymphocytes to mitogens were higher in the winter than in the summer. Natural killer cell activity also varied with season. Cortisol and leptin secretion exhibited circannual rhythms, rising in concert with decreasing photoperiod and increasing testicular activity in the fall. Conversely, prolactin levels declined with decreasing photoperiod and then rose in the spring. CONCLUSION: Neonatal exposure of male primates to Ant appears to alter early postnatal programming of immune function. In the rhesus monkey, immune function shows seasonal fluctuations that may be driven by circannual changes in the secretion of immunoactive hormones.