CIRCULATING NEUTROPHILS AND LIVER-INJURY IN RAT MODELS OF EXPERIMENTAL ALCOHOLIC LIVER-DISEASE

The present study examined the relationship between circulating neutro phils and liver injury in two widely used rat models of chronic ethano l administration. Hematological alterations, liver histopathology, and biochemical indices of liver injury were assessed in rats receiving c hronic ethanol by oral liquid diet feeding (Lieber-DeCarli method) or by continuous intragastric infusion (Tsukamoto-French method). Oral ad ministration of ethanol did not affect circulating neutrophil counts, but resulted in minimal liver injury characterized by elevated serum a lanine aminotransferase (79%), increased liver mass (15%), and moderat e steatosis. In contrast, rats receiving ethanol by continuous intraga stric infusion showed an similar to 2-fold increase in circulating neu trophils, and a moderate degree of liver injury, indicated by a 169% e levation of serum alanine aminotransferase and a 2-fold increase in li ver mass. Liver biopsies from these rats showed severe steatosis and s cattered necrotic hepatocytes, and some neutrophil infiltrates. To det ermine whether an increase in the number of circulating neutrophils co uld potentiate liver injury induced by oral ethanol feeding, rats were treated with human recombinant granulocyte colony-stimulating factor at a dose of 100 mu g/kg/day (sc) for 4 days. Treatment with granulocy te colony-stimulating factor resulted in a 6- to 9-fold increase in ci rculating neutrophil counts. Nevertheless, this change did not enhance the minor degree of ethanol-induced liver injury in this model. Our r esults indicate that, whereas neutrophil leukocytosis accompanies more severe manifestations of ethanol hepatotoxicity in rats, this conditi on per se does not directly induce or exacerbate ethanol-induced liver injury.