Atti 77° Congresso Nazionale SISvet

Both humans and dogs suffer from inflammatory bowel disease (IBD), a chronic nonspecific inflammatory condition of the gastrointestinal tract, in the pathogenesis of which dysregulation of the mucosal immune system plays important role [1]. In human IBD-affected patients, a strong association with increased intestinal expression of interleukin 17A (IL-17A) has been demonstrated [2], to such an extent that a therapeutic approach based on the neutralization of this cytokine has been proposed and developed. Data on the association between canine IBD and IL-17A are, by contrast, conflicting. Indeed, previous studies analyzing the cytokine expression at the protein level in the intestinal mucosa of IBD-affected dogs reported either increased [3] or unchanged [4] IL-17A protein expression in comparison with healthy controls. With the aim to shed light on the involvement of IL-17A in canine IBD, the present study used an immunohistochemical procedure to re-evaluate the expression and localization of IL-17A protein in archived duodenal mucosal biopsies that had been collected, after informed owner consent, from 49 canine IBD patients during routine diagnostic endoscopic procedures. Specimens of normal intestinal mucosa obtained post-mortem from 12 dogs euthanized for other medical reasons served as controls. Sections cut from paraffin blocks of formalin-fixed biopsies were stained with a primary antibody directed against human IL-17A (Abcam). Immunoreactivity was detected using a biotinylated secondary antibody, an avidin-biotinylated peroxidase complex and the peroxidase substrate diaminobenizidine (Vector Laboratories). By means of a computer-aided imaging system (Leica Application Suite), immunopositive cells were counted in properly selected digital fields of the immunostained sections, and cell counts were compared between the two study groups by the non parametric Mann-Whitney U test (with level of significance set at P<0.05). In all of the duodenal samples examined, mononucleated IL-17A expressing cells were present, showing cytosolic positivity, plasmacytoid morphology (consistent with lymphocyte and macrophage phenotype) and scattered distribution mainly in the connective tissue of the lamina propria. However, these cells were very few in numbers, with no significant differences between diseased and control dogs. In conclusion, our results provide evidence that canine IBD, unlike human IBD, is not associated with increased intestinal mucosal expression of IL-17A, corroborating the existence of differences in the immunopathological basis of the two conditions and the preference accordingly assigned to the term immunosuppressant-responsive enteropathy (IRE) when referring to IBD in dogs [1]. Moreover, given the recent demonstration that IL-17A may exert a protective role in human IBD [5], our findings inspire new potential pharmacological approaches to the treatment of canine IBD (IRE).