The effect of age and gender on cytokine production by human peripheral blood mononuclear cells and markers of bone metabolism

Background. Aging has been associated with various alterations of immune functions, the musculoskeletal system and a decline of sex hormone levels. Estradiol has a central role in the regulation of bone turnover and also modulates the production of cytokines such as interleukin-1 and -6 and tumor necrosis factor-a. We therefore studied the effect of age and gender on cytokine production by mononuclear cells and markers of bone metabolism. Methods. Peripheral blood mononuclear cells were isolated from young and elderly subjects; intracellular detection of cytokine production after stimulation with ionomycine and PMA (T cells) or LPS (monocytes) was performed by four color flow cytometry. Sex hormone levels and markers of bone metabolism were measured by RIA or ELISA. Results. When we compared elderly to young women we found an increased proportion of T cells that were positive for interferon-g, interleukin-2, -4, -10 and -13. Also the percentage of cells producing interleukin-4 or interferon-g within the CD8 þ population was higher in the group of elderly women. In contrast, proportionally fewer monocytes of elderly women were positive for tumor necrosis factor-a or interleukin-6 than those of young women. In elderly men a higher percentage of T cells produced interleukin-2, -4 and -13. In the group of aged men we found a higher frequency of cells that produced interleukin-4 within the CD4 þ or CD8 þ population. Moreover, within monocytes of elderly men we found an increased percentage of cells positive for both interleukin-1b and tumor necrosis factor-a. The data on markers of bone metabolism indicated an increase of bone turnover in old age. Conclusion. Our data demonstrate that aging is associated with significant alterations of bone metabolism and cytokine production by T cells and monocytes. For particular cytokines (interferon-g and interleukin-10 in T cells, interleukin-6 and tumor necrosis factor-a in monocytes) these changes are gender specific.