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GWI was linked with exposure to chemicals including the nerve gas prophylactic drug pyridostigmine-bromide (PB) and pesticides (DEET, permethrin). Veterans with GWI exhibit prolonged, low-level systemic inflammation, though whether this impacts the liver is unknown. While no evidence exists that GWI-related chemicals are hepatotoxic, the prolonged inflammation may alter the liver\u2019s response to insults such as cholestatic injury. We assessed the effects of GWI-related chemicals on macrophage infiltration and its subsequent influence on hepatic cholestasis. Sprague Dawley rats were treated daily with PB, DEET and permethrin followed by 15\u2009minutes of restraint stress for 28 days. Ten weeks afterward, GWI rats or na\u00efve age-matched controls underwent bile duct ligation (BDL) or sham surgeries. Exposure to GWI-related chemicals alone increased IL-6, and CD11b<jats:sup>+<\/jats:sup>F4\/80<jats:sup>\u2212<\/jats:sup> macrophages in the liver, with no effect on biliary mass or hepatic fibrosis. However, pre-exposure to GWI-related chemicals enhanced biliary hyperplasia and fibrogenesis caused by BDL, compared to na\u00efve rats undergoing the same surgery. These data suggest that GWI patients could be predisposed to developing worse liver pathology due to sustained low-level inflammation of the liver when compared to patients without GWI.<\/jats:p>","DOI":"10.1038\/s41598-018-31599-9","type":"journal-article","created":{"date-parts":[[2018,8,28]],"date-time":"2018-08-28T12:03:01Z","timestamp":1535457781000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Gulf war illness-related chemicals increase CD11b\/c+ monocyte infiltration into the liver and aggravate hepatic cholestasis in a rodent model"],"prefix":"10.1038","volume":"8","author":[{"given":"Anca D.","family":"Petrescu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie","family":"Grant","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriel","family":"Frampton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5980-0921","authenticated-orcid":false,"given":"Matthew","family":"McMillin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Kain","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maheedhar","family":"Kodali","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5049-6671","authenticated-orcid":false,"given":"Ashok K.","family":"Shetty","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharon","family":"DeMorrow","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2018,9,3]]},"reference":[{"key":"31599_CR1","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1001\/jama.280.11.981","volume":"280","author":"K Fukuda","year":"1998","unstructured":"Fukuda, K. et al. 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