Rat strain differences In TNBS-induced colitis: the antibody and cytokine profile behind the superior survival of albino oxford rats

Inflammatory bowel disease is a chronic intestinal inflammation resulting from host-microbial interactions in a genetically susceptible individual. Two rat strains, Albino Oxford and Dark Agouti, differ in gut microbiota composition and the overall intensity of inflammatory responses. We investigated whether trinitrobenzenesulfonic acid-induced colitis in these two rat strains may be useful for studying therapies for colitis. Male Albino Oxford and Dark Agouti rats were intrarectally injected with trinitrobenzenesulfonic acid and clinically evaluated for 7 days. Colon tissue, peritoneal cavity and mesenteric lymph node cells were analyzed for nitric oxide, urea and cytokine production. The phenotype of peritoneal cavity and lymph node cells was determined by flow cytometry. Dark Agouti rats exhibited higher mortality following colitis induction compared to Albino Oxford rats, accompanied by the extended segments of colon necrosis/inflammation and superior relative balance of IL-17A/IFN-γ in colon tissue and lymph node cells. An increased proportion of neutrophils and diminished proportion of macrophages in peritoneal cavity, and vigorous peritoneal cavity cell IL-6 response was also observed in Dark Agouti rats. Conversely, Albino Oxford rats displayed a higher proportion of peritoneal cavity resident macrophages and lymphocytes from lymph nodes, and dramatically increased production of peritoneal cavity cell IL-10 and urea. Genetically determined inflammatory phenotype of Dark Agouti rats, in contrast to less Inflammatory character of Albino Oxford rats, may serve as a useful model for investigating therapies targeting inflammatory processes in colitis. The use of rats with distinctive inflammatory characteristics may point to specific molecular targets in non-responsive individuals. Clinical trial number: not applicable.