Postmenopausal changes in production of type 1 and type 2 cytokines and the effects of hormone replacement therapy

Objective: An appropriate defense against infective agents or malignant cel ls is attributed to the exquisitely balanced T helper 1 type (cellular) and T helper 2 type (humoral) immune reactions. We investigated the effect of hormone replacement therapy (HRT) on postmenopausal changes in the producti on of interferon (IFN)-gamma and interleukin (IL)-10, a type 1 and a type 2 cytokine, respectively. Design: Both cytokines were measured by ELISA in the supernatant of lipopol ysaccharide-stimulated whole blood cells from 72 untreated and 44 HRT-treat ed women. Thirteen women were examined before and during HRT. Results: The production of IFN-gamma in women in their 40s and in postmenop ausal women was significantly higher compared with that of younger women. H owever, IFN-gamma fell to the lowest level in the late postmenopausal stage , whereas the production of IL-10 increased gradually with age and in paral lel with the postmenopausal period. Thus, in women in the mid- and late pos tmenopausal period, excessive production of type 2 cytokine (IL-10) compare d with type 1 cytokine (IFN-gamma) occurred. The IFN-gamma levels of women on HRT were significantly lower than those of untreated women in the early and mid-postmenopausal stages, and IL-10 levels of women on HRT were signif icantly lower than those of untreated women in the mid- and late postmenopa usal stages. HRT induced a significant decrease in the production of IL-10 and tended to lower the level of IFN-gamma. Conclusions: Production of IL-10 is augmented in postmenopausal women. HRT probably prevents postmenopausal women from an aberration of the immune sys tem by improving the balance of type 1 and type 2 immune reactions.