The effect of the gender factor on multiple sclerosis and autoimmunity

Abstract

Although the etiopathogenesis of multiple sclerosis (MS), as an autoimmune disease, is still unclear, T and B lymphocytes, natural killer (NK) cells, macrophages and cytokines are known to play an important role in attack-remission periods and in progression. The risk of developing an autoimmune disease is greater in women than in men. T helper 1 (Th1) cell activity is in the forefront in MS, and Th1 cell response in women is more dominant than in men. This partly explains why MS and the like autoimmune diseases are more prevalent in women. Low estrogen levels increase Th1-type pro-inflammatory response, while high estrogen and progesterone levels increase Th2-type response. Flare-ups in MS attacks before menstruation and very low estrogen and progesterone levels have been determined in women. The level of attacks decreases significantly in the third trimester of pregnancy during which the progesterone and estrogen are very high, while the incidence and severity of attacks increase in the postnatal period. Progesterone reduces reactive gliosis, increases remyelination and lowers microglial inflammatory activation. Estrogen reduces pro-inflammatory signals. Relapsing remitting MS is more common in women, while more serious disability and a more rapid transition to the progressive form are observed in men. Less inflammatory activity is observed at magnetic resonance imaging in men, while black hole, an indicator of axonal loss and neurodegeneration, more frequently, is more commonly encountered. These clinical and radiological variations support the idea of sex hormones to have an affect on the pathology of MS.