Ethanol-induced CXC-chemokine synthesis and barrier dysfunction in intestinal epithelial cells.
BACKGROUND
Ethanol exposure contributes to infectious complications in burn and trauma patients through a process known as "bacterial translocation." Two major factors, 1) physical disruption of the intestinal mucosal barrier and 2) suppression of immune defense, explain this phenomenon. However, little information is available concerning the immune mechanisms of ethanol-induced bacterial translocation. In this study we investigated the effect of physiological concentrations of ethanol on immune function, especially on CXC-chemokine secretion, neutrophil migration, and barrier function in the small intestine


METHODS
A rat small intestinal intestinal cell line (IEC-18 cells) was exposed to 50-500 mM ethanol for 24 hr with or without IL-1 beta. Secretion of CXC chemokines (GRO/CINC-1 and MIP-2) was measured by ELISA assay, and barrier dysfunction was assessed by the apical-to-basolateral flux of HRP-dextran. Neutrophil transmigration was assessed by enzyme histochemistry (AS-D chloroesterase staining)


RESULTS
Exposure to ethanol concentrations of 200 mM and over increased GRO/CINC-1 secretion, and MIP-2 secretion increased at 500 mM. Administration of ethanol in combination with IL-1 beta had no additive effect on the release of GRO/CINC-1 and MIP-2. Exposure of IEC-18 monolayers to ethanol resulted in a dose-dependent increase in permeability but IL-1 beta had no effect on barrier function. Ethanol had no effect on neutrophil migration in enzyme histochemistry analysis


CONCLUSIONS
The above observations suggest that ethanol induced physical disruption of the intestine but not neutrophil transmigration is the main cause of the bacterial translocation that leads to bacteremia and endotoxemia in alcoholics.
Kishikawa
Hiroshi
H
Department of Gastroenterology, Tokyo Dental College, Ichikawa General Hospital, Chiba, Japan. hkishikaw@syd.odn.ne.jp
Miura
Soichiro
S
Nishida
Jiro
J
Nakano
Masaru
M
Hirano
Erika
E
Sudo
Nao
N
Morishita
Tetsuo
T
Ishii
Hiromasa
H
D000435:Alcoholic Intoxication / Q000378:metabolism; D000465:Algorithms; D000818:Animals; D018988:Bacterial Translocation / Q000187:drug effects; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D019743:Chemokines, CXC / Q000096:biosynthesis*; D016207:Cytokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D007375:Interleukin-1 / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007421:Intestine, Small / Q000166:cytology / Q000187:drug effects / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000187:drug effects; D051381:Rats; D013778:Tetrazolium Salts; D013844:Thiazoles
D002492:Central Nervous System Depressants; D019743:Chemokines, CXC; D016207:Cytokines; D007375:Interleukin-1; D013778:Tetrazolium Salts; D013844:Thiazoles; D000431:Ethanol; C022616:thiazolyl blue