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PubMed2003

Validation of the interleukin-10 knockout mouse model of colitis: antitumour necrosis factor-antibodies suppress the progression of colitis.

Advances in understanding pathogenesis and developing new therapies are hastened by the use of effective animal models of disease. In inflammatory bowel disease, such as Crohn's disease, a variety of models have been used, including the IL-10 knockout mouse. However, in order to be truly valuable, the models need to respond to existing therapy in a way which resembles the human disease. In the light of recent developments, in which refractory Crohn's disease responds well to anti-TNF antibody therapy, we set out to validate the IL-10 knockout model of Crohn's disease by examining its response to anti-TNF therapy. We developed a new scoring system for IL-10 knockout mice, similar to the Crohn's Disease Activity Index in humans, analysed stool samples for cytokines and compared the findings with histology. We found that anti-TNF antibody therapy starting at 4 weeks markedly ameliorated the disease, as judged by the clinical score or by histological analysis of the gut. Furthermore, analysis of stool samples for cytokines revealed a marked diminution of inflammatory cytokines, adding a further accurate measure of the improvement. This model may thus be useful for evaluating other therapeutic modalities of relevance to Crohn's disease.

Animals↗
PubMed2000

Crohn's colitis-like changes in sigmoid diverticulitis specimens is usually an idiosyncratic inflammatory response to the diverticulosis rather than Crohn's colitis.

The clinical outcome and optimum classification of patients who have sigmoid resection specimens that show the histologic features of Crohn's disease (CD) and diverticulitis is not well defined. Historically, these patients were considered to have coexistent diseases, but recent studies have suggested that the CD-like changes are part of the inflammatory reaction of the diverticulitis. Sorting out these issues has been complicated by the lack of distinction between patients with and without CD in other regions of the bowel, short clinical follow-up periods, and small numbers of patients. We report on the clinical outcome and histology of 29 patients who had sigmoid resection specimens with diverticulitis and CD-like changes. Of the 25 patients who had no prior or concurrent CD at the time of surgery, 23 remained free of CD during the follow-up period (median, 6.0 yrs) and two developed CD in other regions of the bowel. All four patients with CD prior to their sigmoid resection continued to have active CD postoperatively. There were no histologic features of the sigmoid resection specimens that could be associated with the outcome of the patient. These results suggest that CD-like changes within the sigmoid resection specimen are an idiosyncratic inflammatory response to the diverticulosis rather than coexistent CD in the overwhelming majority of patients who do not have prior or concurrent CD at the time of sigmoid resection. Pathologists should be wary about making the diagnosis of sigmoid CD in the context of diverticulitis unless there is CD in other parts of the bowel.

Adult↗