Androgens and estrogens modulate the immune and inflammatory responses in rheumatoid arthritis.
Generally, androgens exert suppressive effects on both humoral and cellular immune responses and seem to represent natural anti-inflammatory hormones; in contrast, estrogens exert immunoenhancing activities, at least on humoral immune response. Low levels of gonadal androgens (testosterone/dihydrotestosterone) and adrenal androgens (dehydroepiandrosterone and its sulfate), as well as lower androgen/estrogen ratios, have been detected in body fluids (that is, blood, synovial fluid, smears, salivary) of both male and female rheumatoid arthritis patients, supporting the possibility of a pathogenic role for the decreased levels of the immune-suppressive androgens. Several physiological, pathological, and therapeutic conditions may change the sex hormone milieu and/or peripheral conversion, including the menstrual cycle, pregnancy, the postpartum period, menopause, chronic stress, and inflammatory cytokines, as well as use of corticosteroids, oral contraceptives, and steroid hormonal replacements, inducing altered androgen/estrogen ratios and related effects. Therefore, sex hormone balance is still a crucial factor in the regulation of immune and inflammatory responses, and the therapeutical modulation of this balance should represent part of advanced biological treatments for rheumatoid arthritis and other autoimmune rheumatic diseases.
Cutolo
Maurizio
M
Laboratory and Division of Rheumatology, Department of Internal Medicine and Medical Specialities, University of Genova, Genova, Italy. mcutolo@unige.it
Seriolo
Bruno
B
Villaggio
Barbara
B
Pizzorni
Carmen
C
Craviotto
Chiara
C
Sulli
Alberto
A
D000728:Androgens / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D001327:Autoimmune Diseases / Q000276:immunology / Q000503:physiopathology*; D003278:Contraceptives, Oral, Hormonal / Q000009:adverse effects / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D004967:Estrogens / Q000009:adverse effects / Q000502:physiology*; D005260:Female; D020249:Hormone Replacement Therapy / Q000009:adverse effects; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D008297:Male; D008593:Menopause; D008597:Menstrual Cycle / Q000502:physiology; D051379:Mice; D008954:Models, Biological; D010586:Phagocytes / Q000187:drug effects / Q000276:immunology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000276:immunology / Q000503:physiopathology; D011644:Puerperal Disorders / Q000276:immunology / Q000503:physiopathology; D013312:Stress, Physiological / Q000150:complications / Q000378:metabolism; D013582:Synovial Fluid / Q000166:cytology / Q000378:metabolism
D000728:Androgens; D003278:Contraceptives, Oral, Hormonal; D016207:Cytokines; D004967:Estrogens