Ethanol-induced inhibition of cytokine release and protein degranulation in human neutrophils.
Ethanol impairs immune responses in humans and animal models, in vivo and in vitro. In particular, ethanol inhibits some key functions of human polymorphonuclear neutrophils (PMN). We investigated the impact of ethanol on cytokine production by highly purified PMN. In a time- and concentration-dependent manner, ethanol inhibited the production of interleukin (IL)-8 protein and mRNA and also hindered tumor necrosis factor alpha (TNF-alpha) release by modulating the expression of the TNF-alpha-converting enzyme involved in TNF-alpha shedding. This disruption of PMN cytokine release by ethanol may contribute to the increased risk of infection in alcoholic patients. Degranulation of hepatocyte growth factor (HGF) was also impaired by a clinically relevant ethanol concentration (0.8%), an action that may delay the repair of alcoholic liver damage. These findings suggest that ethanol may modulate three major cytokines involved in alcoholic liver diseases, IL-8, TNF-alpha, and HGF, via three different mechanisms.
Taïeb
Julien
J
Service d'Immunologie et d'Hématologie et INSERM U479, CHU Xavier Bichat, Paris, France.
Delarche
Charlotte
C
Ethuin
Fréderic
F
Selloum
Saphia
S
Poynard
Thierry
T
Gougerot-Pocidalo
Marie-Anne
MA
Chollet-Martin
Sylvie
S
D015550:Cell Degranulation / Q000187:drug effects; D016207:Cytokines / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol; D017228:Hepatocyte Growth Factor