Role of Estrogen Receptor Expression in Estrogen (E-2)-Induced Modulation of Th1 and Th2 Cytokine Responses

Previous studies have demonstrated that repeated administration of 17β-estradiol (E-2) at a dose of 1mg/kg to both (SWR x NZB)F1 (SNF1) mice and (DBA x BALB/c)F1(DBF1) mice resulted in significantly decreased survival and increased appearance of lupus nephritis pathology. However, the ways in which estrogen modulates immune responses has yet to be fully understood, specifically in regard to modulations in TH1 and TH2 cytokine profile. Various studies have reported the presence of two estrogen receptors (ER), a and b, which have been found to be constitutively expressed in many immune cells. In the present project, ER chimeric alpha knockout (αERKO), beta knockout (βERKO) and double knockout (αβERKO) as well as wild type(WT) mice were injected monthly with β-estradiol 17-valerate (E-2) at 1mg/kg. Control mice of each type received oil vehicle only. Results showed that TH1 cytokine production by cells from WT mice was suppressed by E-2 administration, although IFN-γ production was increased in cells from βERKO mice treated with estrogen compared to those treated with oil vehicle. TH2 cytokine production was increased in cells from WT mice treated with estrogen compared to controls. Increases in the production of anti-double stranded DNA antibodies were also observed in cells from αERKO mice. These observations suggest a role for differences in ER-α and ER-β expression in E-2 induced modulation of immune responses, including autoimmune diseases like Systemic Lupus Erythematosus (SLE)