Protective capacity of a IgM/IgA-enriched polyclonal immunoglobulin-G preparation in endotoxemia

Abstract

Animal experiments were carried out to investigate whether a protective effect can be achieved in endotoxemia by intravenous (i.v.) application of a polyclonal immunoglobulin preparation (IVIG-IgG/A/M) enriched with 12% IgM and 12% IgA. Following administration of IVIG-IgG/A/M (500 mg/kg), endotoxemia was induced by intraperitoneal inoculation of a sublethal dose (5 x 108 CFU/kg) of Escherichia coli (E. coli) and subsequent i.v. administration of an antimicrobial agent (Imipenem). Plasma endotoxin activity, IL-6 activity, mean arterial pressure, and skeletal muscle oxygen pressure (tpO2) were measured at regular intervals over a total observation period of 7 h. Prophylactic administration of IVIG-IgG/A/M was found to significantly attenuate (P < 0.01) the antibiotic-induced increase in endotoxin activity as compared to the albumin control group. Limited endotoxemia in the IgG/A/M group was associated with reduced levels of circulating IL-6 (P < 0.01). Both lipopolysaccharide-induced hypotension and depression of tissue oxygenation were attenuated (P < 0.01) by pre-treatment with IVIG-IgG/A/M. The experimental results suggest that in endotoxemia the polyclonal immunoglobulin preparation has a prophylactic protective effect on the acute phase responses and reduces the cardiodepressant effects of E. coli septicaemia.