Chronic inflammatory disorders of the gastrointestinal tract of companion animals.
In the inflammatory bowel diseases (IBD) that affect dogs and cats there appears to be dysregulation of normal mucosal immunity, characterised by polyclonal lymphocytic infiltrates which are presumably specific for luminal antigens. There is an absence of a classical polarisation of either T-helper (Th) 1 or Th2 cytokine responses, although increased expression of mRNA for interleukin (IL) 2 and IL-12p40 and a shift towards mucosal immunoglobulin (Ig) G production are consistent findings, whilst variable responses are seen in tumour necrosis factor-alpha (TNF-alpha), IL-1, IL-4, IL-6, and interferon-gamma (IFN-gamma). Increased mucosal permeability and deranged intestinal motility are common sequelae. Despite obvious similarities with Crohn's disease and ulcerative colitis in humans, important differences exist. Of these, the diffuse superficial nature but with no Th1 or Th2 bias, and the prevalence of proximal small intestinal disease are notable. Potential hypotheses for these disparities include specific differences in the types or locations of agonistic gut flora, diffuse abnormalities in microbial-host interactions, a greater importance of diet, or anatomical or cellular differences in mucosal immune responses. Although specific pathogens and genetic susceptibilities may be involved, quantitative or qualitative changes in the normal flora or abnormal responses to a normal flora are more likely to be involved in the immunopathogenesis. Dietary influences include a large source of antigen, promotion of abnormal microbial growth through Maillard compounds within canned diets, and specific macro- and micronutrient deficiencies. Although dependent on a histopathological diagnosis, limitations of biopsies procured endoscopically, lack of histopathological standardisation and difficulty distinguishing inflammation from neoplasia remain significant problems. Clinician-pathologist dialogue, immunohistochemistry, cytokine profiling and lymphocyte clonality assessment may lead to more accurate diagnoses, a deeper understanding of the immunopathogenesis, and ultimately to new therapies or prevention of disease induction.
Cave
N J
NJ
Center for Companion Animal Health, University of California, Davis, CA 95616, USA. njcave@ucdavis.edu