{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T05:44:54Z","timestamp":1761975894489,"version":"build-2065373602"},"reference-count":127,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T00:00:00Z","timestamp":1620345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["U01 AA017347","U01 AA013521","R01 AA005965","R37 AA010723"],"award-info":[{"award-number":["U01 AA017347","U01 AA013521","R01 AA005965","R37 AA010723"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Classical inflammation in response to bacterial, parasitic, or viral infections such as HIV includes local recruitment of neutrophils and macrophages and the production of proinflammatory cytokines and chemokines. Proposed biomarkers of organ integrity in Alcohol Use Disorders (AUD) include elevations in peripheral plasma levels of proinflammatory proteins. In testing this proposal, previous work included a group of human immunodeficiency virus (HIV)-infected individuals as positive controls and identified elevations in the soluble proteins TNF\u03b1 and IP10; these cytokines were only elevated in AUD individuals seropositive for hepatitis C infection (HCV). The current observational, cross-sectional study evaluated whether higher levels of these proinflammatory cytokines would be associated with compromised brain integrity. Soluble protein levels were quantified in 86 healthy controls, 132 individuals with AUD, 54 individuals seropositive for HIV, and 49 individuals with AUD and HIV. Among the patient groups, HCV was present in 24 of the individuals with AUD, 13 individuals with HIV, and 20 of the individuals in the comorbid AUD and HIV group. Soluble protein levels were correlated to regional brain volumes as quantified with structural magnetic resonance imaging (MRI). In addition to higher levels of TNF\u03b1 and IP10 in the 2 HIV groups and the HCV-seropositive AUD group, this study identified lower levels of IL1\u03b2 in the 3 patient groups relative to the control group. Only TNF\u03b1, however, showed a relationship with brain integrity: in HCV or HIV infection, higher peripheral levels of TNF\u03b1 correlated with smaller subcortical white matter volume. These preliminary results highlight the privileged status of TNF\u03b1 on brain integrity in the context of infection.<\/jats:p>","DOI":"10.3390\/ijms22094953","type":"journal-article","created":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T10:06:12Z","timestamp":1620381972000},"page":"4953","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Preliminary Evidence for a Relationship between Elevated Plasma TNF\u03b1 and Smaller Subcortical White Matter Volume in HCV Infection Irrespective of HIV or AUD Comorbidity"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3346-4894","authenticated-orcid":false,"given":"Natalie M.","family":"Zahr","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA"},{"name":"Neuroscience Program, SRI International, Menlo Park, CA 94025, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5416-5159","authenticated-orcid":false,"given":"Kilian M.","family":"Pohl","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA"},{"name":"Neuroscience Program, SRI International, Menlo Park, CA 94025, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allison J.","family":"Kwong","sequence":"additional","affiliation":[{"name":"Gastroenterology and Hepatology Medicine, Stanford University School of Medicine, Stanford, CA 94350, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6739-3716","authenticated-orcid":false,"given":"Edith V.","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Neuroscience Program, SRI International, Menlo Park, CA 94025, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adolf","family":"Pfefferbaum","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA"},{"name":"Neuroscience Program, SRI International, Menlo Park, CA 94025, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1037\/neu0000557","article-title":"Brain-behavior relations and effects of aging and common comorbidities in alcohol use disorder: A review","volume":"33","author":"Sullivan","year":"2019","journal-title":"Neuropsychology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1002\/hep.30587","article-title":"A Call to Standardize Definitions, Data Collection, and Outcome Assessment to Improve Care in Alcohol-Related Liver Disease","volume":"70","author":"Shen","year":"2019","journal-title":"Hepatology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/BF01991779","article-title":"An international perspective on the prevalence of the Wernicke-Korsakoff syndrome","volume":"10","author":"Harper","year":"1995","journal-title":"Metab. 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