Sex hormones as immunomodulators in health and disease

In addition to their effects on sexual differentiation and reproduction, se x hormones influence the immune system. This results in a gender dimorphism in the immune function with females having higher immunoglobulin levels an d mounting stronger immune responses following immunization or infection th an males. The greater immune responsiveness in females is also evident in t heir increased susceptibility to autoimmune diseases. However, a clear unde rstanding of the myriad of effects that sex hormones have on the immune sys tem is lacking. Studies in normal mice show that estrogen treatment induces polyclonal B cell activation with increased expression of autoantibodies c haracteristic of autoimmune diseases. Several mechanisms appear to contribu te to the break in tolerance and the increase in plasma cell activity inclu ding a reduction of the mass of the bone marrow and the thymus, the emergen ce of sites of extrameduallary hematopoiesis and altered susceptibility of B cells to cell death. In addition, sex hormone levels in both humans and e xperimental models correlated with the activity of their cytokine-secreting cells indicating that sex hormones influence the cytokine milieu and sugge sting that altered sex hormonal levels in autoimmune patients contribute to the skewed cytokine milieu characteristic of systemic lupus erythematosus (SLE). While sex hormones alone do not cause autoimmune disease, abnormal hormone levels may provide the stage for other factors (genetic, infectious) to tri gger disease. Understanding the physiology of the interaction between sex h ormones and immune function and its potential pathological consequences may provide insight into the autoimmune diseases and new directions for their treatment. Published by Elsevier Science B.V.