Estrogen inhibits systemic T cell expression of TNF-α and recruitment of TNF-α⁺ T cells and macrophages into the CNS of mice developing experimental encephalomyelitis

Estrogen treatment has been found to have suppressive activity in several models of autoimmunity. To investigate the mechanism of 17β-estradiol (E2) suppression of experimental autoimmune encephalomyelitis, we evaluated E2 effects on TNF-α expression in the central nervous system (CNS) and spleen of C57BL/6 mice immunized with MOG 35-55/CFA. Kinetic analysis demonstrated that E2 treatment drastically decreased the recruitment of total inflammatory cells as well as TNF-α⁺ macrophages and T cells into the CNS at disease onset. In contrast, E2 had only moderate effects on the relatively high constitutive TNF-α expression by resident CNS microglial cells. E2 treatment also had profound inhibitory effects on expression of TNF-α by splenic CD4⁺ T cells, including those responsive to MOG 35-55 peptide. We propose that the mechanism of E2 protection may involve both systemic inhibition of TNF-α expression and local (CNS) recruitment of inflammatory cells, with modest effects on TNF-α expression by resident CNS microglial cells.