Immunomodulatory effects of estrogen and progesterone replacement in a nonhuman primate model

A novel postmenopausal nonhuman primate model consisting of healthy young and old ovariectomized rhesus macaques was used to assess the short-term immunomodulatory effects of transdermally administered estrogen and progesterone. Specifically, we determined estrogen- and progesterone-induced changes in absolute numbers of circulating lymphocytes (B lymphocytes, CD4(+) lymphocytes, and CD8(+) lymphocytes) as well as lymphocytes expressing the activation markers CD25 and CD69. In addition, we assessed B and T lymphocyte activity, i.e, immunoglobulin (Ig) and interferon-gamma (IFN-gamma) production by peripheral blood mononuclear cells (PBMCs). In general, treatment with estrogen or progesterone resulted in decreased lymphocyte numbers and in down-modulation of activation markers. In addition, hormone replacement resulted in a decreasing trend for PBMC IFN-gamma production, whereas PBMC Ig production was minimally affected. Hormone treatment seemed to influence young and old animals differently, with the young animals appearing more susceptible to its immune system-related effects. These results indicate that, in our animal model exogenously administered hormones may dynamically interact with the immune system, resulting in in vivo modulation of lymphocyte numbers and activity.