Cytokines and alcohol.
Cytokines are multifunctional proteins that play a critical role in cellular communication and activation. Cytokines have been classified as being proinflammatory (T helper 1, Th1) or anti-inflammatory (T helper 2, Th2) depending on their effects on the immune system. However, cytokines impact a variety of tissues in a complex manner that regulates inflammation, cell death, and cell proliferation and migration as well as healing mechanisms. Ethanol (alcohol) is known to alter cytokine levels in a variety of tissues including plasma, lung, liver, and brain. Studies on human monocyte responses to pathogens reveal ethanol disruption of cytokine production depending upon the pathogen and duration of alcohol consumption, with multiple pathogens and chronic ethanol promoting inflammatory cytokine production. In lung, cytokine production is disrupted by ethanol exacerbating respiratory distress syndrome with greatly increased expression of transforming growth factor beta (TGFbeta). Alcoholic liver disease involves an inflammatory hepatitis and an exaggerated Th1 response with increases in tumor necrosis factor alpha (TNFalpha). Recent studies suggest that the transition from Th1 to Th2 cytokines contribute to hepatic fibrosis and cirrhosis. Cytokines affect the brain and likely contribute to changes in the central nervous system that contribute to long-term changes in behavior and neurodegeneration. Together these studies suggest that ethanol disruption of cytokines and inflammation contribute in multiple ways to a diversity of alcoholic pathologies.
Crews
Fulton T
FT
Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, North Carolina 27599-7178, USA. ftcrews@med.unc.edu
Bechara
Rabih
R
Brown
Lou Ann
LA
Guidot
David M
DM
Mandrekar
Pranoti
P
Oak
Shilpa
S
Qin
Liya
L
Szabo
Gyongyi
G
Wheeler
Michael
M
Zou
Jian
J
D000437:Alcoholism / Q000150:complications / Q000276:immunology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000502:physiology*; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008104:Liver Cirrhosis, Alcoholic / Q000276:immunology; D008171:Lung Diseases / Q000209:etiology / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000502:physiology
D016207:Cytokines; D008070:Lipopolysaccharides; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol