Ethanol inhibits IgE-induced degranulation and cytokine production in cultured mouse and human mast cells.
Activated mast cells (MC) can produce a wide variety of potent inflammatory mediators. Excessive alcohol consumption is known to lead to immune deficiency and propensity for pneumonias in particular. As MCs are important in the first line of defence of mucosal membranes we have studied the effect of ethanol (EtOH) on several MC functions. EtOH attenuated dose dependently IgE-induced degranulation of mouse bone marrow derived mast cells (mBMMC) as reflected by the release of granule associated beta-hexosaminidase (beta-hex). A mean of 26 +/- 7% inhibition of beta-hex release was observed in the presence of 5/1000 (86 mM) EtOH and nearly complete inhibition in the presence of 20/1000 (344 mM) ethanol. The IgE-induced degranulation of mBMMC cultured with EtOH for seven days was inhibited to a similar degree as the degranulation of mBMMC exposed to EtOH for only one hour. Inclusion of 5/1000 (86 mM) ethanol in the medium reduced tumour necrosis factor (TNF)-alpha and interleukin (IL)-8 production in human mast cell line (HMC-1) cells by 55 +/- 7% and 19 +/- 5%, respectively, and the presence of 20/1000 (344 mM) ethanol inhibited the expression 81 +/- 12% and 59 +/- 14% respectively. These results suggest that, in contrast to previous assumption, ethanol inhibits several critical MC functions at least in vitro. This inhibition of mediator, and cytokine release in particular, could contribute to the immune deficiency associated with chronic alcohol consumption.
Toivari
M
M
Institute of Biomedicine, Department of Medical Chemistry, University of Helsinki, Finland.
Mäki
T
T
Suutarla
S
S
Eklund
K K
KK
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D000001:Calcimycin / Q000494:pharmacology; D015550:Cell Degranulation / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D003594:Cytoplasmic Granules / Q000201:enzymology; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D007073:Immunoglobulin E / Q000494:pharmacology*; D016209:Interleukin-8 / Q000096:biosynthesis; D007700:Kinetics; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000494:pharmacology; D019089:Stem Cell Factor / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D001619:beta-N-Acetylhexosaminidases / Q000032:analysis
D016207:Cytokines; D016209:Interleukin-8; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D014409:Tumor Necrosis Factor-alpha; D007073:Immunoglobulin E; D000001:Calcimycin; D000431:Ethanol; D001619:beta-N-Acetylhexosaminidases; D013755:Tetradecanoylphorbol Acetate