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However, these findings remain largely correlational in clinical samples. Therefore, we conducted a preliminary inflammatory challenge using endotoxin in individuals with alcohol use disorder (AUD) to investigate the immune, behavioral, and brain responses to the inflammatory challenge.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Participants were randomly assigned to receive a bolus intravenous injection of either low\u2010dose endotoxin (0.8\u2009ng\/kg of body weight) or placebo (same volume of 0.9% saline). Blood samples, sickness symptoms, physiology, mood, and alcohol craving were collected at baseline and hourly for 4\u2009h postbaseline, with a neuroimaging scan occurring at 3\u2009h postbaseline. Matched control data were used to validate the endotoxin challenge in comparison to the AUD sample.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Endotoxin led to an acute blunted pro\u2010inflammatory (i.e., TNF\u2010\u03b1, IL\u20106, and IL\u20108) response in individuals with AUD compared to controls (all <jats:italic>p'<\/jats:italic>s\u2009&lt;\u20090.039). Endotoxin led to decreased cue\u2010induced craving in both the behavioral human laboratory (<jats:italic>p<\/jats:italic>\u2009=\u20090.03) and neuroimaging (<jats:italic>p'<\/jats:italic>s\u2009&lt;\u20090.01) assays. Moreover, higher levels of endotoxin\u2010induced IL\u20106 were most negatively associated with decreased self\u2010reported craving following baseline (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) in comparison with lower levels of endotoxin\u2010induced IL\u20106.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This preliminary study provides an acute experimental manipulation of inflammatory processes associated with AUD and suggests that the short\u2010term effects of inflammation in AUD phenomenology are multifaceted and dose\u2010dependent.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.70090","type":"journal-article","created":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T22:54:55Z","timestamp":1748818495000},"page":"1473-1488","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Inflammatory endotoxin challenge in individuals with alcohol use disorder and controls"],"prefix":"10.1111","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1594-7796","authenticated-orcid":false,"given":"Kaitlin R.","family":"McManus","sequence":"first","affiliation":[{"name":"Department of Psychology University of California, Los Angeles  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5528-4918","authenticated-orcid":false,"given":"Erica N.","family":"Grodin","sequence":"additional","affiliation":[{"name":"Department of Psychology University of California, Los Angeles  Los Angeles California USA"},{"name":"Department of Psychiatry and Biobehavioral Sciences University of California, Los Angeles  Los Angeles California USA"},{"name":"Brain Research Institute University of California, Los Angeles  Los Angeles California USA"},{"name":"Cousins Center for Psychoneuroimmunology University of California, Los Angeles  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Burnette","sequence":"additional","affiliation":[{"name":"Neuroscience Interdepartmental Program University of California, Los Angeles  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yenashi","family":"Castillo","sequence":"additional","affiliation":[{"name":"Department of Psychology University of California, Los Angeles  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"Miotto","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Biobehavioral Sciences University of California, Los Angeles  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael R.","family":"Irwin","sequence":"additional","affiliation":[{"name":"Department of Psychology University of California, Los Angeles  Los Angeles California USA"},{"name":"Department of Psychiatry and Biobehavioral Sciences University of California, Los Angeles  Los Angeles California USA"},{"name":"Cousins Center for Psychoneuroimmunology University of California, Los Angeles  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naomi","family":"Eisenberger","sequence":"additional","affiliation":[{"name":"Department of Psychology University of California, Los Angeles  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5734-9444","authenticated-orcid":false,"given":"Lara A.","family":"Ray","sequence":"additional","affiliation":[{"name":"Department of Psychology University of California, Los Angeles  Los Angeles California USA"},{"name":"Department of Psychiatry and Biobehavioral Sciences University of California, Los Angeles  Los Angeles California USA"},{"name":"Brain Research Institute University of California, Los Angeles  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,6]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11481\u2010009\u20109185\u2010z"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2020.08.002"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alcohol.2014.10.002"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000045669.16499.ec"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0096864"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0112050"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2015.09.001"},{"key":"e_1_2_10_9_1","doi-asserted-by":"crossref","unstructured":"Beck A.T. 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