Effects of human i.v. immunoglobulin on bacterial clearance and granulocyte function in endotoxinemia

Abstract

The therapeutic impact of intravenous immunoglobulins (ivIG) in septic patients remains controversial. Until now, the mechanisms of action have not been fully elucidated. Since polymorphonuclear neutrophils (PMN) play a key role in host defence, this study focuses on the effects of ivIG on bacterial clearance and PMN respiratory burst activity during endotoxinaemia. For this purpose, it was investigated whether ivIG improves blood clearance and organ colonisation as well as PMN functions after experimentally induced bacteraemia in rabbits. The experiments were performed in 30 anaesthetised rabbits. To determine quantification of bacterial killing in vivo, defined numbers of exogenous Escherichia (E.) coli 1.3 x 10(8) CFU) were injected intravenously in untreated animals (n = 10) or 60 min after infusion of endotoxin (LPS: 40 micrograms/kg/h) in groups without (n = 10), and after pretreatment with ivIG (Sandoglobulin, 0.5 g/kg body weight, n = 10), respectively. Parameters monitored were rates of bacterial elimination from the blood, LPS clearance, arterial pressure, blood gases and white blood cell counts, PMN burst activity was determined using a flow cytometry assay. Samples of liver, kidney, spleen and lung were collected for bacterial counts 180 min following E. coli injection. Compared to controls, endotoxinaemia resulted in a prolonged elimination of the injected E. coli out of the blood associated with a significantly (p < 0.01) higher colonisation of all organs. Pretreatment with ivIG improved LPS clearance and significantly reduced bacterial colonisation of lung and kidney (p < 0.01). This was paralleled by an enhanced PMN respiratory burst activity compared to untreated animals (p < 0.05). The reduced bacterial colonisation of lung and kidney in correlation with an increased PMN bactericidal activity in endotoxinaemia suggest an improved granulocyte-dependent bacterial killing due to ivIG application.