EFFECT OF ANTIALLERGIC AGENTS ON CHEMOTAXIS OF NEUTROPHILS BY STIMULATION OF CHEMOTACTIC FACTOR RELEASED FROM HEPATOCYTES EXPOSED TO ETHANOL

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.