Endotoxaemia and cytokine production in experimental colitis

Systemic endotoxaemia is a well recognized feature of inflammatory bowel disease but its pathogenic role remains uncertain. This study examined plasma endotoxin and cytokine concentrations and the acute-phase protein response in a hapten-induced model of experimental colitis. On days 2, 8 and 14 after induction of colitis with trinitrobenzenesulphonic acid in ethanol (TNBS-E), plasma endotoxin, immunoglobulin (Ig) G and IgM endotoxin-core antibody (EndoCAb), tumour necrosis factor (TNF), interleukin (IL) 6 and alpha 2-macroglobulin (alpha 2M) concentrations and colon macroscopic inflammation score were determined. At all time points there was significant colonic inflammation when compared with control values (P < 0.0001). Animals treated with TNBS-E had raised concentrations of endotoxin at all time points (P < 0.04). In TNBS-E-treated animals EndoCAb concentrations were reduced on day 2 (P < 0.0001) and later increased. There were increases in IL-6 and alpha 2M concentrations in TNBS-E-treated animals but no significant change in TNF concentrations. Endotoxin concentrations correlated with macroscopic inflammation score, IL-6 and alpha 2M concentrations. There was a less consistent correlation between EndoCAb concentrations and these parameters. These results suggest that endotoxin is a mediator of the systemic response in this model of experimental colitis.