In vivo effects of sex steroids on lymphocyte responsiveness and immunoglobulin levels in humans

The female predominance in several autoimmune diseases suggests a role for sex steroid hormones in disease susceptibility. We therefore investigated t o what extent sex hormones would influence immune responsiveness. me analyz ed T helper type 1 (T(H)1) and type 2 cytokine patterns, chemokine receptor expression (n = 2 x 10), and Ig levels (n = 2 x 25) in transsexual men and women before and after 4 months of cross-sex hormone administration. Antit hyroperoxidase levels mere compared between 186 transsexual males (treated >5 yr with estrogens) and 186 male controls. In men, estrogens plus antiandrogens increased free cortisol levels in 24-h urine samples, decreased natural killer cell numbers, and slightly inhibit ed the mitogen-induced interferon-gamma/interleukin-4 ratio, but up-regulat ed the expression of T(H)1-associated chemokine receptors, CCR1, CXCR3, and CCR5, Conversely, in women, androgens slightly decreased free cortisol lev els in 24-h urine samples and enhanced the mitogen-induced interferon-gamma /interleukin-4 ratio and tumor necrosis factor-alpha production. At the sin gle cell level no T(H)1/T(H)2 shifts were found. Remarkably, up-regulation of T(H)1 cytokines was accompanied by down-regulation of CCR1, CXCR3, and C CR5 expression. Neither CD4(+) lymphocyte numbers nor IgG, IgM, and antithy roperoxidase levels, although higher in women then in men, were affected by cross-sex hormonal treatment. These results demonstrate that the capacity to develop a T(H)1 phenotype of peripheral blood lymphocytes is stimulated by androgens and is slightly in hibited by estrogens. These changes may be direct or indirect through the e ffects on other hormones.