title: Prognostic Significance of the Systemic Inflammatory and Immune Balance in Alcoholic Liver Disease with a Focus on Gender-Related Differences.
abstract: OBJECTIVE
  Mechanisms of immune regulation in alcoholic liver disease (ALD) are still unclear. The aim of our study was to determine an impact of Th17 / regulatory T (Treg) cells balance and its corresponding cytokine profile on the ALD outcome. Possible gender-related differences in the alcohol-induced inflammatory response were also assessed.
  
  
  METHODS
  147 patients with ALD were prospectively recruited, assigned to subgroups based on their gender, severity of liver dysfunction and presence of ALD complications at admission, and followed for 90 days. Peripheral blood frequencies of Th17 and Treg cells together with IL-1beta, IL-6, IL-17A, IL-23, and TGF-beta1 levels were investigated. Flow cytometry was used to identify T cell phenotype and immunoenzymatic ELISAs for the corresponding cytokine concentrations assessment. Multivariable logistic regression was applied in order to select independent predictors of advanced liver dysfunction and the disease complications.
  
  
  RESULTS
  IL-17A, IL-1beta, IL-6 levels were significantly increased, while TGF-beta1 decreased in ALD patients. The imbalance with significantly higher Th17 and lower Treg frequencies was observed in non-survivors. IL-6 and TGF-beta1 levels differed in relation to patient gender in ALD group. Concentrations of IL-6 were associated with the severity of liver dysfunction, development of ALD complications, and turned out to be the only independent immune predictor of 90-day survival in the study cohort.
  
  
  CONCLUSIONS
  We conclude that IL-6 revealed the highest diagnostic and prognostic potential among studied biomarkers and was related to the fatal ALD course. Gender-related differences in immune regulation might influence the susceptibility to alcohol-associated liver injury.
authors.affiliation: Department of Gastroenterology with Endoscopy Unit, Medical University of Lublin, Lublin, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Kasztelan-Szczerbińska
authors.affiliation: Department of Clinical Immunology, Medical University of Lublin, Lublin, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Surdacka
authors.affiliation: Department of Gastroenterology with Endoscopy Unit, Medical University of Lublin, Lublin, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Celiński
authors.affiliation: Department of Clinical Immunology, Medical University of Lublin, Lublin, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Roliński
authors.affiliation: Medical University of Lublin, Lublin, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Zwolak
authors.affiliation: Department of Gastroenterology, Provincial Specialist Hospital, Lublin, Poland.
authors.forename: Sławomir
authors.initials: S
authors.lastname: Miącz
authors.affiliation: Department of Gastroenterology with Endoscopy Unit, Medical University of Lublin, Lublin, Poland.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Szczerbiński
mesh_terms: D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000276:immunology / Q000473:pathology; D015850:Interleukin-6 / Q000097:blood* / Q000276:immunology; D008099:Liver / Q000276:immunology / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000097:blood* / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012727:Sex Characteristics; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology / Q000473:pathology
chemical_list: D016207:Cytokines; D015850:Interleukin-6