Depletion of neutrophils and modulation of Kupffer cell function in allyl alcohol-induced hepatotoxicity

Abstract

The roles of neutrophils (PMNs) and Kupffer cells in hepatotoxicity caused by allyl alcohol in rats in vivo were examined. To test the involvement of PMNs in the response to allyl alcohol, the number of circulating PMNs was reduced to < 500/μl by treatment with immunoglobulin (Ig) isolated from serum of rabbits treated with rat PMNs (anti-PMN Ig). Rats received anti-PMN Ig or control Ig 6 h before and 6 h after administration of allyl alcohol (40 mg/kg, i.p.). Hepatotoxicity was assessed 18 h after allyl alcohol administration. In rats pretreated with control Ig, treatment with allyl alcohol resulted in hepatotoxicity as evidenced by an increase in the activity of alanine aminotransferase (ALT) in serum. Neutropenia did not attenuate hepatic injury caused by allyl alcohol. Leukopenia induced by pretreatment with cyclophosphamide also did not influence the hepatotoxic response to allyl alcohol. To inhibit the function of Kupffer cells, animals were treated with gadolinium chloride (GdCl 3; 10 mg/kg, i.v.) 24 h before administration of allyl alcohol. This dose of GdCl 3 decreased in situ clearance of colloidal carbon by 64%. Despite the inhibition of Kupffer cell function, ALT activity in serum was not different in allyl alcohol-treated rats pretreated with GdCl 3 and those pretreated with saline vehicle. Histopathologic evaluation of the livers confirmed a lack of protective effect of GdCl 3. These results suggest that neither neutrophils nor Kupffer cells play a major role in liver injury due to allyl alcohol.