The phytoestrogen genistein suppresses cell-mediated immunity in mice

Abstract

The soy phytoestrogen, genistein, induces thymic atrophy when administered to ovariectomized mice by injection or in the diet. Injected genistein also causes decreased humoral immunity, but the effects of genistein on cellmediated immunity have not been addressed. Here we examined effects of injected and dietary genistein on cell-mediated immune responses. Female C57BL/6 mice (25-to 27-days-old) were ovariectomized, then placed on phytoestrogen-free feed 5 days later. Seven days after ovariectomy, they were given daily subcutaneous injections of either dimethylsulfoxide (DMSO) or genistein (8, 20, 80 mg/kg) for 28 days; some mice were given 80 mg/ kg genistein plus the anti-estrogen ICI 182,780 (5 mg/ kg/week). Cell-mediated immune response was tested by analyzing the delayed-type hypersensitivity (DTH) response to a hapten, 4-hydroxy-3-nitrophenyl acetyl succinimide (NP-O-SU), at the end of treatment. Reversibility of the effects of genistein was tested by measuring the DTH response in mice that were given genistein (20 or 80 mg/kg) for 28 days, then allowed to recover for 28 days. To determine if dietary genistein could affect cell-mediated immunity, mice ovariectomized as above were fed genistein at 0, 1000 or 1500 parts per million (ppm) for 28 days. There was a 46-67% decrease in the DTH response in the footpads of mice injected with 8-80 mg/kg genistein compared with controls (P<0·05 vs control for all treatment groups); these effects were reversible. On histopathological examination of the feet, there was decreased cell infiltration in genistein-treated animals compared with controls, and the numbers of CD4 + and CD8 + T cells in popliteal lymph nodes were reduced. The effects of genistein are mediated through both estrogen receptor (ER) and non-ER pathways, as the anti-estrogen ICI 182,780 only partially blocked the effects of genistein on the DTH response. Dietary genistein (1000 or 1500 ppm) decreased cellmediated immunity while producing serum genistein concentrations in the physiological range for humans under certain nutritional conditions. Further work is needed to determine if dietary genistein and phytoestrogen exposure can produce effects on cell-mediated immunity in humans or other animals under various nutritional conditions.

Phytoestrogens

“…Injection of genistein into ovariectomized adult mice at a concentration that produced similar serum genistein levels to those reported in soy-fed human infants resulted in significant loss of weight of the thymus gland, apoptosis of thymocytes leading to drastically reduced thymocyte numbers, changes in spleen cell numbers, and reduced humoral immunity (199). In a subsequent study, the same treatment reduced cellular immunity (200). In both studies, the effects of genistein were concluded to occur through ER-dependent and independent pathways.…”

Endocrine disrupters – potential modulators of the immune system and allergic response

“…Isoflavones were shown to affect chemotactic factors production (60-62), oxygen radical generation (63)(64)(65)(66), adhesion molecule expression (67-69) and alter arachidonic acid metabolism (70)(71)(72), compatible with their anti-inflammatory effects. Dietary and injected genistein suppressed cell-mediated immunity in mice even at levels similar to those obtained in human diet (73). As cell activity recovered to normal after the treatment was stopped, it has been suggested that immune changes caused by genistein may be reversible.…”

Soy isoflavones and immunity

“…Delayed -type hypersensitivity (DTH) reaction is classified as type IV allergy response and is mainly mediated by T cells and macrophages. Genistein suppresses DTH reaction to oxazolone and granulocyte -mediated response (15). In addition to cellular immune response, genistein also suppresses antigen (Ag) -induced antibody (Ab) production.…”