{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T07:07:40Z","timestamp":1779088060650,"version":"3.51.4"},"reference-count":67,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100018784","name":"Foundation of Hope for Research and Treatment of Mental Illness","doi-asserted-by":"publisher","award":["2022 \u20101"],"award-info":[{"award-number":["2022 \u20101"]}],"id":[{"id":"10.13039\/100018784","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alcohol, Clinical and Experimental Research"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Alcohol use disorder (AUD) lacks objective clinical tests; current screening (AUDIT) relies on self\u2010report and can miss risk. Building on our recent whole\u2010blood analysis, where immune dysregulation, particularly IL\u20101\u03b2, predicted AUD risk, we tested whether Toll\u2010like receptor (TLR) stimulation would further unmask risk\u2010related immune signatures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Whole blood from 28 young adults (Low\u2010risk: AUDIT &lt;6; High\u2010risk: AUDIT \u22656) was stimulated in culture with lipopolysaccharide (LPS, TLR4) or imiquimod (IMQ, TLR7). Fourteen immune mediators were quantified using Luminex multiplex assays. Group and stimulus effects were tested with aligned rank transform (ART) factorial models; principal component analysis (PCA) summarized the multivariate structure. Predictive associations with AUDIT were assessed via linear regression and Random Forest analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      IL\u20101\u03b2, IL\u20103, IL\u20106, IL\u20107, IL\u20108, IL\u201018, CCL11, MCP\u20101, and MIP\u20101\u03b2 were elevated in the high\u2010risk group following stimulation. LPS evoked stronger responses than IMQ for IL\u20101\u03b2, IL\u20106, IL\u20108, and MIP\u20101\u03b2, whereas MCP\u20101 was higher with IMQ. PCA distinguished high\u2010 from low\u2010risk groups, driven by CCL11, MCP\u20101, IL\u20107, IL\u20103, IL\u20106, IL\u201018, MIP\u20101\u03b2, and IL\u20101\u03b2. LPS\u2010evoked IL\u20101\u03b2, IL\u20103, and CCL11 predicted AUDIT scores (adjusted\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090.22\u20130.37). IMQ\u2010evoked CCL11, IL\u201018, MIP\u20101\u03b2, IL\u20101\u03b2, and IL\u20106 were also significant predictors (adjusted\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090.16\u20130.29). After outlier filtering, LPS associations persist, and IMQ\u2010evoked CCL11 and IL\u201018 remain. Random Forests predicted AUDIT with\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090.33 (LPS) and\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090.27 (IMQ), with top features IL\u20103, IL\u201018, IL\u20101\u03b2, CCL11 (LPS) and IL\u20106, IL\u201018, CCL11, IL\u20101\u03b2 (IMQ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>LPS and IMQ stimulations unmasked immune response patterns that separated high\u2010 from low\u2010risk individuals, with exaggerated pro\u2010inflammatory responses in the high\u2010risk group. IL\u20101\u03b2, IL\u20103, IL\u201018, and CCL11 repeatedly predicted AUDIT scores, with IL\u20101\u03b2 and IL\u20103 LPS\u2010dominant and CCL11 and IL\u201018 LPS\/IMQ stimulus\u2010shared. Stimulation\u2010evoked mediator profiling may complement self\u2010report screening and improve risk stratification in drinkers. Further studies are needed to address the exploratory nature of the results.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/acer.70236","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T10:01:26Z","timestamp":1770112886000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lipopolysaccharide and imiquimod stimulation of potential immune biomarkers in whole blood predict alcohol use disorder risk based on\n                    <scp>AUDIT<\/scp>\n                    scores"],"prefix":"10.1111","volume":"50","author":[{"given":"Irina","family":"Balan","sequence":"first","affiliation":[{"name":"Bowles Center for Alcohol Studies, School of Medicine The University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"},{"name":"Department of Psychiatry, School of Medicine The University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alejandro G.","family":"Lopez","sequence":"additional","affiliation":[{"name":"Bowles Center for Alcohol Studies, School of Medicine The University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"},{"name":"Department of Biochemistry and Biophysics University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas A.","family":"Gilmore","sequence":"additional","affiliation":[{"name":"Bowles Center for Alcohol Studies, School of Medicine The University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"},{"name":"Department of Psychiatry, School of Medicine The University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael P.","family":"Bremmer","sequence":"additional","affiliation":[{"name":"Department of Psychology The University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8723-734X","authenticated-orcid":false,"given":"Todd K.","family":"O'Buckley","sequence":"additional","affiliation":[{"name":"Bowles Center for Alcohol Studies, School of Medicine The University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, School of Medicine The University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian S.","family":"Hendershot","sequence":"additional","affiliation":[{"name":"Bowles Center for Alcohol Studies, School of Medicine The University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"},{"name":"Department of Psychiatry, School of Medicine The University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4441-956X","authenticated-orcid":false,"given":"A. 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