Experimental gut-derived endotoxaemia and bacteraemia are reduced by systemic administration of monoclonal anti-LPS antibodies

Abstract

This study aimed to investigate the effects and mechanisms of action of systemic administration of monoclonal antibodies, anti-endotoxin (HA-1A), in an animal model of gut-origin sepsis. In the first experiment, Balb c mice were transfused with allogeneic blood ( C3H HeJ mice). Five days post-transfusion the animals were gavaged with 1 × 10 9 Escherichia coli and randomized into three groups ( n = 22 each) to receive a sham burn (SB group) or a 20 per cent TBSA thermal injury, immediately followed by the systemic administration of monoclonal antibodies (3 mg/kg) (HA-1A group) or aliquots of sterile saline (Control group). The animal survival rate was observed for 10 days poslburn. In the second experiment transfusion and burn injury were reproduced but the mice ( n = 8/group) were gavaged with 10 9 E.coli labelled with 111indium oxine. Four hours after the burn the mesenteric lymph nodes, liver, lungs and blood were harvested to determine plasma endotoxin levels and the magnitude of translocation of labelled bacteria measured by the residual radioactivity in the organs. Circulating endotoxin levels were determined by limulus assay. The mortality rate of the HA-1A group (9 per cent) was similar to the SB group (0 per cent) and significantly lower than the control group (59 per cent) ( P < 0.05). Both plasma endotoxin levels and degree of bacterial translocation in all extraintestinal tissues were significantly lower (by approximately 50 per cent) in the HA-1A group than in the control group ( P < 0.05). Systemic administration of HA-1A exerts a beneficial effect by reducing the circulating levels of endotoxin and by increasing the gut barrier function to translocating microorganisms.