COX-2 and 5-LO enzyme levels in dogs with chronic gut disease

Abstract

BACKGROUND: Cyclooxygenase-2 (COX-2) is a key enzyme in the synthesis of pro-inflammatory prostaglandins and 5-lipoxygenase (5-LO) is the major source of leukotrienes. Their role in IBD has been demonstrated in humans and animal models, but not in dogs with chronic enteropathies (CCE). HYPOTHESIS: COX-2 and 5-LO are upregulated in dogs with CCE. ANIMALS: Fifteen healthy control dogs (HCD), 10 dogs with inflammatory bowel disease (IBD), and 15 dogs with food-responsive diarrhea (FRD). METHODS: Prospective study. mRNA expression of COX-2, 5-LO, IL-1b, IL-4, IL-6, TNF, IL-10 and TFG-&#x3b2; was evaluated by quantitative real-time RT-PCR in duodenal and colonic biopsies before and after treatment. RESULTS: COX-2 expression in the colon was significantly higher in IBD and FRD before and after treatment (all P < .01). IL-1b was higher in FRD in the duodenum after treatment (P = .021). TGF-&#x3b2; expression was significantly higher in the duodenum of HCD compared to FRD/IBD before treatment (both P < .001) and IBD after treatment (P = .012). There were no significant differences among groups and within groups before and after treatment for IL-4, IL-6, TNF, and IL-10. There was a significant correlation between COX-2 and IL-1b in duodenum and colon before treatment in FRD and IBD, whereas 5-LO correlated better with IL-6 and TNF. IL-10 and TGF-&#x3b2; usually were correlated. CONCLUSIONS AND CLINICAL IMPORTANCE: COX-2 is upregulated in IBD and FRD, whereas IL-1b and TGF-&#x3b2; seem to be important pro- and anti-inflammatory cytokines, respectively. The use of dual COX/5-LO inhibitors could be an interesting alternative in the treatment of CCE.