Chapter 50 - Hormones and Cytokines: Gender-Specific Effects

Abstract

Sex hormones can exert local actions (intracrine) in the tissues in which they are formed and an accelerated peripheral metabolic conversion of upstream androgen precursors to 17β-estradiol and even conversion to more estrogenic metabolites is observed in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients. The circadian rhythms of cortisol and melatonin circadian rhythms are altered, at least in RA, and these alterations also partially involve circadian synthesis and levels of sex hormones. Local effects of sex hormones in autoimmune rheumatic diseases seem to consist mainly of modulation of cell proliferation and cytokine production and may also affect the development and activation of specific mature B cell subsets. In this respect, it is interesting that male patients with RA seem to profit more from anti-TNF-α treatment strategies than do female patients. In fact, blockade of TNF-induced upregulation of aromatase would particularly increase the level of androgens in male as compared with female patients with RA, and this can lead to the better clinical outcome that has already been reported in male patients. Certainly, endogenous and exogenous hormones have great potential to affect the immune system and can change activity of autoimmune diseases, and it is worthwhile to continue to seek novel and improved applications of hormonal or/and antihormonal immunotherapy (i.e. antiestrogens, receptor modulators, antagonist metabolites, androgenic compounds) to treating this family of diseases. In conclusion, sex hormones play a role in the genesis of autoimmunity and future research may provide a therapeutic approach that is capable of altering disease pathogenesis, rather than targeting disease sequelae.