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Do sex hormones modulate the synovial macrophages in rheumatoid arthritis?
  1. Division of Rheumatology, Department of Internal Medicine, University of Genova, Italy
  1. Dr M Cutolo, Via D Chiodo 25 c/7, 16136 Genova, Italy

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It is becoming apparent that various host influences are important determinants in the development of autoimmune diseases, including rheumatoid arthritis (RA).

The organism responds to inflammatory stimula with coordinated series of adaptive responses involving the immune, nervous, and endocrine systems.

Although immunogenetics may dominate the susceptibility to develop the disease, the most powerful additional factor recognised in the host is the sex of the patient.

Recent epidemiological, clinical, and laboratory evidence has suggested that sex hormones play a central part in the immune response and the immune mediated pathological conditions.1

Overall, women have greater humoral and cellular immune responses and therefore may be more susceptible than men to autoimmune diseases, including RA. Women have higher immunoglobulin concentrations than men and produce greater antibody responses to various microorganisms after immunisation. Cell mediated immune response is also stronger in women as shown by a more efficient rejection of allografts and relative resistance to immunotolerance.2

On the other hand, women have greater plasma corticotropin (ACTH) response to ovine corticotropin release hormone (CRH) and more prolonged increases in cortisol values, thus indicating CRH neuron activation by oestradiol.1 Conversely, androgens inhibit the hypothalamic-pituitary-adrenal axis (HPA) supporting the complex interactions existing between the immune response and neuroendocrine system.

In synthesis, evidence suggests that physiological concentrations of oestrogens stimulate while male hormones suppress the immune response.

As the distinct female preponderance in autoimmune diseases exists mainly during the reproductive ages, sex hormone concentrations and metabolism have been evaluated in the affected patients (that is, RA, systemic lupus erythematosus (SLE)) and have often been found to be changed.

In particular, low gonadal and adrenal androgens (testosterone (Tes)/dihydrotestosterone (DHT) and dehydroepiandrosterone sulphate (DHEAS), respectively), as well as reduced androgens/oestrogens ratio, have been detected in male and female RA patients, suggesting a reduction of the related immunosuppressive …

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