Induction of iNOS in a rat model of acute colitis

Induction of colitis by 2,4,6-Trinitrobenzenesulphonic acid (TNB) in the ra t is a widely used experimental model of inflammatory bowel disease. Action of TNB as a hapten, induces colitis involving infiltration of colonic muco sa by neutrophils and macrophages and increased production of inflammatory mediators. The aim of the present study was to measure nitric oxide synthas e (NOS) activity and characterize relations between inducible NOS (iNOS) ac tivity and other signs of inflammation in TNB-induced colitis. A profound a nd sustained increase in the activity of INOS was found in the colon. The a ctivity of NOS in the spleen was also increased, but remained at low levels as compared to those in colon. No increases in plasma nitrite + nitrate co ncentrations were found suggesting local rather than systemic induction of iNOS. The increase in iNOS activity in the colon was preceded by macroscopi c inflammatory lesions, like hyperemia, ulcerations and edema formation as well as neutrophil accumulation in the gastric mucosa and increased circula ting concentrations of PGE(2) metabolite (PGEM). Concentrations of PGEM in the plasma and myeloperoxidase activity (MPO; marker of neutrophil infiltra tion) in the gut declined in 48h whereas increased iNOS activity and the ma croscopic inflammatory lesions remained over the 72h follow-up period. The results demonstrate increased local iNOS activity in TNB-Induced colitis mi micking the situation in human inflammatory bowel disease.