EXPERIMENTAL GUT-DERIVED ENDOTOXEMIA AND BACTEREMIA ARE REDUCED BY SYSTEMIC ADMINISTRATION OF MONOCLONAL ANTI-LPS ANTIBODIES

This study aimed to investigate the effects and mechanisms of action o f 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). Fi ve days post-transfusion the animals were gavaged with I x 10(9) Esche richia coil and randomized into three groups (n = 22 each) to receive a sham burn (SB group) or a 20 per cent TBSA thermal injury, immediate ly followed by the systemic administration of monoclonal antibodies (3 mg/kg) (HA-1A group) or aliquots of sterile saline (Control group). T he animal survival rate was observed for 10 days postburn. In the seco nd experiment transfusion and burn injury were reproduced but the mice (n = 8/group) were gavaged with 10(9) E.coli labelled with (111)indiu m oxine. Four hours after the burn the mesenteric lymph nodes, liver, lungs and blood were harvested to determine plasma endotoxin levels an d the magnitude of translocation of labelled bacteria measured by the residual radioactivity in the organs. Circulating endotoxin levels wer e determined by limulus assay. The mortality rate of the HA-IA group ( 9 per cent) tons similar to the SE group (0 per cent) and significantl y lower than the control group (59 per cent) (P<0.05). Both plasma end otoxin levels and degree of bacterial translocation in all extraintest inal tissues were significantly lower (by approximately 50 per cent) i n the HA-IA group than in the control group (P<0.05). Systemic adminis tration of HA-IA exerts a beneficial effect by reducing the circulatin g levels of endotoxin and by increasing the gut barrier function to tr anslocating microorganisms.