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 responsi ble for this remains unknown. To determine whether neutrophils play an y role in producing this depression, hepatocellular function was measu red in neutrophil-competent and neutropenic animals subjected to sepsi s. Neutropenia was induced by tail vein injection of an immuno-globuli n 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 m odel of polymicrobial sepsis). Neutropenia was confirmed by peripheral blood smears. Neutrophil-competent controls were given nonimmunized I g before the onset of sepsis. Sham-operated animals received anti-neut rophil Ig or control Ig. Hepatocellular function [i.e., the maximal ve locity of indocyanine green clearance (V-max) and efficiency of the cl earance (K-m)] was determined by a fiber-optic catheter and in vivo he moreflectometer 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 depre ssed during early sepsis. The depression in V-max and K-m was, however , prevented by neutrophil depletion, suggesting an integral role of th e neutrophils in depressing hepatocellular function under such conditi ons. The results suggest that the prudent modulation of neutrophil fun ction during the early stage of polymicrobial sepsis may be beneficial for preventing or delaying the occurrence of hepatocellular dysfuncti on. (C) 1997 Academic Press.