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Abstract
Endocrine–immune system interactions are the basis for predominance of autoimmune diseases in women with differences between the fertile and the postmenopausal periods. B cell-driven diseases reach the maximum incidence rate in the reproductive years, at least in women under the effects of serum estrogens and their metabolites (endocrine synthesis). On the other hand, the prevalent peripheral synthesis of estrogens, especially in advanced ages (intracrine synthesis), through the action of aromatases, modulate the immune/inflammatory response in peripheral tissues similarly in both female and male patients (final common pathway). Interestingly, tissue injury that occurs during chronic immune/inflammatory reaction induces tissue repair and homeostatic responses including cell proliferation, growth factor production and angiogenesis that might facilitate cancer progression. The successful treatment of chronic immune/inflammatory diseases obtained by using medications initially developed for use in oncology, such as antiproliferative drugs, B-cell depleting monoclonal antibodies support the inflammation–cancer link.
Financial & competing interests disclosure
No financial and competing interests disclosures are reported by the authors related to the materials discussed in the manuscript. All the authors are members of the EULAR (European League Against Rheumatism) Study Group on Neuroendocrine Immunology without any economical support or competing interests. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
Key issues
The predominance of autoimmune diseases in women is mainly linked to the endocrine–immune system interactions with differences between the fertile and the postmenopausal periods.
Based on the hormonal changes, in particular estrogens and their metabolites (endocrine), B cell-driven diseases reach the maximum incidence rate in the reproductive years, at least in women.
The prevalent peripheral synthesis of estrogens, especially in advanced ages (intracrine synthesis), through the action of aromatase, modulate the immune/inflammatory response in peripheral tissues similarly in both female and male patients. The 16-hydroxylated estrogen metabolites are predominant.
Tissue injury that occurs during chronic immune/inflammatory reaction induces tissue repair and homeostatic responses including cell proliferation, mutations, growth factor production and angiogenesis that might facilitate cancer progression.
Immunoglobulin production itself is also seen in those patients who are diagnosed with breast cancer, as well as antibodies against catechol estrogen-modified DNA have been found in the sera of both systemic lupus erythematosus and cancer patients.
The successful treatment of chronic immune/inflammatory diseases obtained by using medications initially developed for use in oncology, such as antiproliferative drugs, B-cell depleting monoclonal antibodies support the chronic inflammation–cancer link.
The circadian increase of growth factors during night hours suggests that cancer patients of both sexes, similar than patients with autoimmune diseases (inflammatory markers also increase at the same time), might profit from night-time treatment strategies.