Cells, cytokines and inflammatory bowel disease: a clinical perspective.
Ulcerative colitis and Crohn's disease are chronic inflammatory disorders of the GI tract. Although the disorders can usually be distinguished on clinical and pathological criteria, there are similarities in natural history and response to therapy. The purpose of this article is to examine the inflammatory infiltrate in both disorders and the cytokine profiles in intestinal mucosa and peripheral blood. For both disorders, the predominant cells in inflamed mucosa are neutrophils and lymphocytes positive for CD4. There are also increases in the number of B cells, macrophages, dendritic cells, plasma cells, eosinophils and perhaps mast cells. Cytokine levels and cytokine expression are also similar for both disorders, with increases in TNF-α and IFN-γ consistent with a Th1 response. As inflammation occurs in a microbial environment, one possibility is that the nature of the inflammatory response is largely independent of initiating factors. One concept that might be useful is that of initiating cells and cytokines and effector cells and cytokines. Persuasive evidence exists for a defect in phagocytic cells in Crohn's disease, perhaps with the expansion of a subset of activated macrophages. There are also possible links to natural killer cells and changes in the regulation of IL-8 and perhaps IL-22. For ulcerative colitis, the cellular events are less clear, but natural killer T cells may be important as initiating cells, and there is some evidence for upregulation of cytokines involved in Th2 responses, including IL-4 and IL-13. For both disorders, proinflammatory cytokines include TNF-α, IL-12, IL-23, and perhaps IL-17 and IFN-γ. Research challenges include the identification, activation and function of subsets of inflammatory cells, as well as new ways to terminate the inflammatory response.
Department of Gastroenterology and Hepatology, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia. ian.roberts-thomson@health.sa.gov.au
Ian C
IC
Roberts-Thomson
James
J
Fon
Wendy
W
Uylaki
Adrian G
AG
Cummins
Simon
S
Barry
D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D003093:Colitis, Ulcerative / Q000378:metabolism* / Q000473:pathology*; D003424:Crohn Disease / Q000378:metabolism* / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D009504:Neutrophils / Q000473:pathology
D016207:Cytokines