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Ovarian hormones in innate inflammation

Journal article
Authors Alexandra Stubelius
Annica Andersson
Ulrika Islander
Hans Carlsten
Published in Immunobiology
Volume 222
Issue 8-9
Pages 878-883
ISSN 0171-2985
Publication year 2017
Published at Institute of Medicine, Department of Rheumatology and Inflammation Research
Centre for Bone and Arthritis Research
Pages 878-883
Language en
Keywords Estrogen, Sex steroids, Ovarian hormones, Macrophages, Acute inflammation, Chemotaxis, estrogen-receptor, rheumatoid-arthritis, sex-differences, in-vivo, macrophages, autoimmunity, activation, expression, promotes, gene, Immunology
Subject categories Rheumatology and Autoimmunity, Obstetrics, Gynecology and Reproductive Medicine


Aim: A more vigorous immune system activation is generally seen in women as compared to men. The reasons for these differences are still not understood. By investigating the immune-regulatory role of estrogens, we have previously shown that estradiol (E2) can regulate and ameliorate rheumatoid arthritis models. The aim of this study was to elucidate the role of ovariectomy (ovx) and estradiol (E2) in innate immune responses. Methods: Female mice were ovx or sham operated. After three weeks, either dorsal air pouches were established by injections of sterile air with subsequent lipopolysaccharide (LPS) injection, or LPS was injected intra-peritoneally (i.p). Mice received daily injections with E2 or vehicle for three days before challenge. 6 hours after challenge in the air pouch, blood cells were counted, leukocytes from the pouch were analyzed by flow cytometry, and cytometric bead array or ELISA were used to quantify cytokines collected from the air pouch. Blood cells were counted 1 h after i.p challenge. Results: Compared to sham, blood leukocyte numbers increased after ovx and ovx + E2 6 h after LPS injections into the air pouch. LPS after ovx induced neutrophil infiltration into the pouch, accompanied by increased levels of MCP-1 and IL-6. Ovx + E2 further enhanced cell infiltration after LPS; however, the cell population diversified by also including more macrophages and monocytes, with reduced MCP-1 and IL-6 levels. Compared to ovx, blood leukocyte numbers increased already 1 h after i.p challenge in ovx + E2 mice. Conclusion: Our findings suggest that ovarian hormones and estradiol can adjust the acute innate immune reaction by regulating cell recruitment to inflammatory sites, diversify the responding cell population, and at the same time down-regulate production of certain pro-inflammatory cytokines. Our results also suggest a faster responding immune system after E2. Our results bring further information into the intricate relationship between inflammation and sex steroids.

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