The role of neutrophils in producing hepatocellular dysfunction during the hyperdynamic stage of sepsis in rats

Although studies have shown that hepatocellular function is depressed during the early, hyperdynamic stage of sepsis, the mechanism responsible for this remains unknown. To determine whether neutrophils play any role in producing this depression, hepatocellular function was measured in neutrophil-competent and neutropenic animals subjected to sepsis. Neutropenia was induced by tail vein injection of an immunoglobulin directly against rat neutrophils (anti-neutrophil Ig) at 16 and 2 h prior to the initiation of cecal ligation and puncture (CLP, i.e., a model of polymicrobial sepsis). Neutropenia was confirmed by peripheral blood smears. Neutrophil-competent controls were given nonimmunized Ig before the onset of sepsis. Sham-operated animals received anti-neutrophil Ig or control Ig. Hepatocellular function [i.e., the maximal velocity of indocyanine green clearance (Vmax) and efficiency of the clearance (Km)] was determined by a fiber-optic catheter and in vivo hemoreflectometer at 5 h after CLP (i.e., early, hyperdynamic sepsis) or sham operation. Serum alanine aminotransferase (ALT) levels were also determined. The results indicate that although circulating levels of ALT were not elevated, hepatocellular function was significantly depressed during early sepsis. The depression in Vmax and Km was, however, prevented by neutrophil depletion, suggesting an integral role of the neutrophils in depressing hepatocellular function under such conditions. The results suggest that the prudent modulation of neutrophil function during the early stage of polymicrobial sepsis may be beneficial for preventing or delaying the occurrence of hepatocellular dysfunction.