17β-estradiol and soy phytochemicals selectively induce a type 2 polarization in mesenteric lymph nodes of ovariectomized rats

Objective: This study was designed to compare the effects of 17 beta-estradiol (17 beta-E-2) and a phytoestrogen-containing soy extract on the immune system in an ovariectomized rat model of menopause. Specifically, T- and B-lymphocyte subsets, the balance of type I and 2 immune responses in the mesenteric lymph nodes, and serum levels of different classes of immunoglobulin were examined as study endpoints. Design: Ovariectomized rats were treated with either the phytoestrogen-containing soy extract (50 or 100 mg/kg/day PO), 17 beta-E-2 (0.5 mg/kg/day PO), or vehicle; a sham control was included in the study. After the rats were killed, mesenteric lymph nodes and blood samples were collected. B- and T (CD4(+) and CD8(+))-lymphocyte subsets in mesenteric lymph nodes were evaluated by flow cytometry analysis. Cytokine-producing T lymphocytes were identified within each T-lymphocyte subset as T(H)1 (interferon-gamma(+) CD4(+)), T(H)2 (interleukin-4(+) CD4(+)), T(C)1 (interferon-gamma(+) CD8(+)), and T(C)2 (interferon-4(+) CD8(+)) lymphocytes. Serum levels of immunoglobulin classes were determined by enzyme-linked immunosorbent assay. Results: There were no differences in the proportions of B lymphocytes and CD4+ and CD8+ T lymphocytes among groups. Treatment with 17 beta-E-2 and phytoestrogen-containing soy extract induced a reduction in T(H)1 and TC1 lymphocytes paralleled by a slight, nonsignificant, increase in the frequency of TH2. Data expressed as T(H)1/T(H)2 and T(C)1/T(C)2 ratios depicted a significant polarization of local immunity toward a Immoral response. Evaluation of immunoglobulin serum levels did not show any significant difference among groups. Conclusions: Here we show that estrogens and soy phytochemicals similarly polarize the immune system toward a type 2 immune response in a preclinical model of menopause; our data draw attention to the crucial need to evaluate in clinical studies the potential side effects on the immune system of the complex soy products that are actually consumed in the postmenopausal setting.