The increasing prevalence of Crohn's disease in industrialized societies: the price of progress?
Crohn's disease (CD) is an idiopathic inflammatory condition of the gastrointestinal system. While inflammation can activate one of a number of specific branches of the immune system, CD promotes a T helper cell type 1 (Th1) profile. The prospect that CD is a form of Th1-dominant autoimmune disease is gaining acceptance, with support from the current use of immunosuppressants. Recently, convincing evidence that the various branches of the immune system have the ability to keep each other in check has suggested that the Th1 profile of CD may stem from a greatly reduced T helper cell type 2 (Th2) immune response. A strong Th2 immune response is a characteristic of the once prevalent enteric parasitic diseases, now nearly eradicated from industrial society. This has led to the acceptance of a hygiene hypothesis, which suggests that the inverse relationship between CD and the level of a society's industrialization is, in fact, causal - that the lack of parasitic infections causes a weakened systemic Th2 cytokine profile, leading to elevated Th1 cytokines and, ultimately, the development of spontaneous Th1-mediated diseases such as CD. Supporting this, it has been recently demonstrated that an experimentally-induced Th2 response can help moderate Th1-dominant events in both animal and human studies. Based on this recent and convincing work, the present review focuses on the role of immunoregulation in the development of CD, with particular emphasis on the potential use of Th2-promoting agents (such as helminths or cytokines) as therapeutics in the treatment or prevention of CD.
Wells
Ron W
RW
Gastrointestinal Diseases Research Unit, Hotel Dieu Hospital, Queen's University, 166 Brock Street, Kingston, Ontario K7L 5G2, Canada.
Blennerhassett
Michael G
MG
D000818:Animals; D001327:Autoimmune Diseases / Q000453:epidemiology; D003424:Crohn Disease / Q000453:epidemiology* / Q000276:immunology; D019049:Developed Countries; D006373:Helminthiasis; D006801:Humans; D015995:Prevalence; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology