Hormones, pregnancy, and autoimmune diseases.
Hormonal factors linked to age, gender, and reproductive status are undoubtedly involved in regulating the onset of numerous autoimmune diseases. For example, systemic lupus erythematosus (SLE), a disease characterized by immune complex-mediated pathology linked to excess Th2 cytokine production (e.g., IL-10) primarily affects women in the reproductive years. Rheumatoid arthritis (RA), a disease characterized primarily by cell-mediated joint immunopathology linked to deficient Th2 cytokine production, is also more common in women, but, in contrast to SLE, the highest incidence is at menopause. Pregnancy-associated changes in these diseases, however, provide the most compelling evidence that hormonal factors play a major role in modulating the expression of these diseases. SLE often flares during pregnancy, whereas RA commonly remits during pregnancy and flares or initially develops in the postpartum period. These observations appear to be explained by the accumulating data indicating that during pregnancy cell-mediated immune function and Th1 cytokine production (e.g., IL-12, interferon-gamma) are suppressed, and humoral immunity and Th2 cytokine production (e.g., IL-4, IL-10) are enhanced. These patterns reverse in the postpartum period. In other words, antithetical Th1/Th2 cytokine profiles appear to characterize pregnancy and the postpartum period. Strong evidence now indicates that changes in the production of cortisol, progesterone, and estrogen play a major role in modulating Th1/Th2 cytokine balance.
Wilder
R L
RL
Inflammatory Joint Diseases Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. wilderr@arb.niams.nih.gov
D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology* / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006728:Hormones / Q000502:physiology*; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology; D049590:Postpartum Period / Q000502:physiology; D011247:Pregnancy / Q000502:physiology*
D016207:Cytokines; D006728:Hormones; D018836:Inflammation Mediators