title: Chronic alcoholism is associated with an imbalanced production of Th-1/Th-2 cytokines by peripheral blood T cells.
abstract: BACKGROUND
  In the present study, we analyzed, at the intracellular level, the pattern of cytokine secretion by the major CD4+ and CD8strong+ peripheral blood (PB) T-cell subsets in patients with chronic alcoholism, and we correlated it both with the ethanol (EtOH) intake status and with the presence or not of alcoholic liver disease.
  
  
  METHODS
  For that purpose, a total of 30 chronic alcoholic patients, 10 without liver disease (AWLD group) and 20 diagnosed with alcoholic liver cirrhosis (ALC) were studied. In all cases, flow cytometric measurement of intracellular expression of interferon-gamma (IFN-gamma), interleukin (IL)-2, and IL-4 was performed on PB CD4+ and CD8strong+ T lymphocytes.
  
  
  RESULTS
  After studying AWLD patients, we found increased numbers of both CD4+ and CD8strong+ PB T cells with detectable cytoplasmic levels of the IL-2 and IFN-gamma T helper (Th)-1-associated cytokines, the greater increase being observed for this latter cytokine (p<0.001 for CD4+ and p<0.01 for CD8strong+ T cells). Regarding ALC patients, the pattern of expression of intracellular cytokines by PB T cells was different depending on the status of EtOH intake at the moment of entering this study. Accordingly, as in AWLD patients, ALC individuals who were actively drinking also displayed increased numbers of both CD4+ and CD8strong+ T cells expressing Th-1-associated cytokines. However, in these patients, expression of IFN-gamma, although being significantly greater than that observed in control individuals (p<0.05), was significantly lower than that in AWLD patients (p<0.01 and p<0.05, for CD4+ and CD8strong+ T cells, respectively). After a withdrawal period of > or =1 yr, ALC patients did not show significant changes in the cytoplasmic expression of Th-1-associated cytokines compared with the control group; in contrast, these patients showed a marked increase on the proportion of CD4+ and CD8strong+ T cells expressing IL-4, a Th-2-associated cytokine (p<0.01). After considering the ratio between the number of T cells expressing Th- (IFN-gamma)- and Th-2 (IL-4)-associated cytokines in each individual, we found that there was a significant imbalance in this ratio, with a predominance of IFN-gamma-producing T cells over IL-4+ T lymphocytes during EtOH intake.
  
  
  CONCLUSIONS
  Our results showed that in patients with chronic alcoholism, active EtOH intake is associated with a Th-1 pattern of cytokine production by PB T cells.
authors.affiliation: Servicio de Medicina Interna II, Hospital Universitario, Salamanca, Spain. laso@gugu.usal.es
authors.forename: F J
authors.initials: FJ
authors.lastname: Laso
authors.forename: C
authors.initials: C
authors.lastname: Iglesias-Osma
authors.forename: J
authors.initials: J
authors.lastname: Ciudad
authors.forename: A
authors.initials: A
authors.lastname: López
authors.forename: I
authors.initials: I
authors.lastname: Pastor
authors.forename: A
authors.initials: A
authors.lastname: Orfao
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000097:blood*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D002492:Central Nervous System Depressants / Q000008:administration & dosage; D000431:Ethanol / Q000008:administration & dosage; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008104:Liver Cirrhosis, Alcoholic / Q000097:blood*; D008222:Lymphokines / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
chemical_list: D002492:Central Nervous System Depressants; D007376:Interleukin-2; D008222:Lymphokines; D000431:Ethanol; D007371:Interferon-gamma