PMID- 28554684 OWN - NLM STAT- MEDLINE DCOM- 20180312 LR - 20180314 IS - 1878-3279 (Electronic) IS - 0171-2985 (Linking) VI - 222 IP - 8-9 DP - 2017 Aug TI - Ovarian hormones in innate inflammation. PG - 878-883 LID - S0171-2985(17)30089-X [pii] LID - 10.1016/j.imbio.2017.05.007 [doi] AB - 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 1h 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 1h 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. CI - Copyright (c) 2017 The Author(s). Published by Elsevier GmbH.. All rights reserved. FAU - Stubelius, Alexandra AU - Stubelius A AD - Centre for Bone and Arthritis Research (CBAR), Department of Rheumatology and In fl ammation Research, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden. Electronic address: Alexandra.Stubelius@rheuma.gu.se. FAU - Andersson, Annica AU - Andersson A AD - Centre for Bone and Arthritis Research (CBAR), Department of Rheumatology and In fl ammation Research, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden. Electronic address: Annica.Andersson@rheuma.gu.se. FAU - Islander, Ulrika AU - Islander U AD - Centre for Bone and Arthritis Research (CBAR), Department of Rheumatology and In fl ammation Research, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden. Electronic address: Ulrika.Islander@rheuma.gu.se. FAU - Carlsten, Hans AU - Carlsten H AD - Centre for Bone and Arthritis Research (CBAR), Department of Rheumatology and In fl ammation Research, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden. Electronic address: Hans.Carlsten@rheuma.gu.se. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170520 PL - Netherlands TA - Immunobiology JT - Immunobiology JID - 8002742 RN - 0 (CD200 receptor, mouse) RN - 0 (Cytokines) RN - 0 (Lipopolysaccharides) RN - 0 (Membrane Glycoproteins) RN - 4TI98Z838E (Estradiol) SB - IM MH - Animals MH - Cytokines/immunology MH - Estradiol/*pharmacology MH - Female MH - Immunity, Innate/drug effects MH - Inflammation/chemically induced/*immunology MH - Leukocyte Count MH - Leukocytes/*drug effects/immunology MH - Lipopolysaccharides MH - Membrane Glycoproteins/immunology MH - Mice, Inbred C57BL MH - *Ovariectomy OTO - NOTNLM OT - Acute inflammation OT - Chemotaxis OT - Estrogen OT - Macrophages OT - Ovarian hormones OT - Sex steroids EDAT- 2017/05/31 06:00 MHDA- 2018/03/13 06:00 CRDT- 2017/05/31 06:00 PHST- 2017/03/27 00:00 [received] PHST- 2017/05/12 00:00 [revised] PHST- 2017/05/14 00:00 [accepted] PHST- 2017/05/31 06:00 [pubmed] PHST- 2018/03/13 06:00 [medline] PHST- 2017/05/31 06:00 [entrez] AID - S0171-2985(17)30089-X [pii] AID - 10.1016/j.imbio.2017.05.007 [doi] PST - ppublish SO - Immunobiology. 2017 Aug;222(8-9):878-883. doi: 10.1016/j.imbio.2017.05.007. Epub 2017 May 20.