ROLE OF HISTAMINE IN A RAT MODEL OF COLITIS

We examined the possible involvement of mast cells in a rat model of c olitis, by monitoring levels of histamine at various times after induc ing inflammation with intrarectal trinitrobenzene sulfonic acid in 50% ethanol. The ability of a histamine HI antagonist, diphenhydramine, t o modify colitis was also assessed. As expected, trinitrobenzene sulfo nic acid in 50% ethanol induced a sustained colitis. Myeloperoxidase l evels in macroscopically damaged tissue peaked at one week, and declin ed thereafter. In contrast, tissue histamine levels were normal at one week, then increased in damaged tissue to approximately four times no rmal levels at four weeks. Indices of inflammation were markedly suppr essed at one week by diphenhydramine, while tissue histamine levels we re unaffected. Chronic colitis in rats is thus apparently accompanied by a local mast cell hyperplasia or influx. Moreover, antagonism of a major mast cell mediator, histamine, significantly reduces the severit y of inflammation in this model.