TH-1 and TH-2 cytokines in stable chronic alcoholics

Alcohol Alcohol. 2012 Jul-Aug;47(4):390-6. doi: 10.1093/alcalc/ags041. Epub 2012 Apr 16.

Abstract

In alcoholics, the activation of Kupffer cells by gram negative bacteriae leads to an inflammatory response and cytokine secretion, which in turn activate T-lymphocytes. Possibly, Th-1 lymphocytes are activated first, followed by a Th-2 response. Th-2 cytokines, especially interleukin (IL)-13 (scarcely studied in alcoholics), may be involved in the progression to chronic stages.

Aims: The aim of the study was to analyze the relationship of Th-1 and Th-2 cytokines with liver function, alcohol consumption, nutritional status and survival.

Methods: Serum Th-1 [interferon-γ (IFN-γ)] and Th-2 cytokines (IL-4, IL-13), IL-10, IL-6 and tumor necrosis factor (TNF-α), were determined for 18 controls and 47 stable alcoholics with variable liver function impairment, who were followed-up during a median time of 90 months, a period during which 14 patients died.

Results: IL-4 was lower among patients; no differences were observed regarding IL-6, but the remaining ILs were higher among alcoholics. IL-10 and IL-13 were even higher in cirrhotics (Z = 2.88, P = 0.004, and Z = 2.09, P = 0.037, respectively). A significant, direct, correlation was observed between IL-13 and IL-10 (ρ = 0.49, P = 0.001), and non-significant, inverse ones were observed between IFN-γ and IL-13 (ρ = -0.23), IL-4 (ρ = -0.14) and IL-10 (ρ = -0.09). IL-13 and IL-10 were inversely related with liver function and, directly with immunoglobulin A levels, but not with survival.

Conclusion: Serum IFN-γ values were increased in alcoholics, who also showed raised IL-13 and IL-10, but lower IL-4 levels. Given the immunomodulatory roles of IL-10 and IL-13, this increase may be interpreted as a compensatory rise of anti-inflammatory cytokines. We failed to find any relation with mortality.

MeSH terms

  • Adult
  • Alcoholism / blood*
  • Alcoholism / complications
  • Alcoholism / mortality
  • Case-Control Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Interferon-gamma / blood*
  • Interleukins / blood*
  • Liver / physiopathology*
  • Liver Cirrhosis, Alcoholic / blood*
  • Liver Cirrhosis, Alcoholic / physiopathology
  • Liver Function Tests
  • Male
  • Middle Aged
  • Nutrition Assessment
  • Statistics, Nonparametric
  • Tumor Necrosis Factor-alpha / blood*

Substances

  • Interleukins
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma