Y. Shiratori et al., EFFECT OF ANTIALLERGIC AGENTS ON CHEMOTAXIS OF NEUTROPHILS BY STIMULATION OF CHEMOTACTIC FACTOR RELEASED FROM HEPATOCYTES EXPOSED TO ETHANOL, Digestive diseases and sciences, 39(7), 1994, pp. 1569-1575
In an attempt to clarify a mechanism of neutrophil infiltration in the
liver of alcoholics and possible therapeutic effect of antiallergic a
gents on accumulation of these cells in the liver, we investigated che
motaxis of neutrophils by stimulation of a chemotactic factor released
from rat hepatocytes exposed to ethanol. When hepatocytes were incuba
ted with more than 30 mM ethanol for 24 hr, chemotactic activity for b
oth rat and human neutrophils was demonstrated in the conditioned medi
um. An enhanced chemotactic activity of the conditioned medium was red
uced in the presence of antibody against KC/gro protein, one of the in
terleukin-8-related cytokines in rodents. Antiallergic agents such as
azelastine or ketotifen at a concentration of >0.01 mu M markedly redu
ced chemotaxis of neutrophils. Prednisolone at a concentration of >10
mu M also reduced chemotaxis of neutrophils. These results suggest tha
t neutrophil accumulation in the liver of human alcoholics could be in
duced by a chemotactic factor produced by the ethanol-treated hepatocy
tes and that antiallergic agents could be effective against the extent
of alcoholic hepatitis by reducing chemotaxis of neutrophils.