Proposed pathogenesis of inflammatory bowel disease and target sites for pharmacological intervention. Shown are the interactions among bacterial antigens in the intestinal lumen and immune cells in the intestinal wall. If the epithelial barrier is impaired, bacterial antigens can gain access to antigen-presenting cells (APC) such as dendritic cells in the lamina propria. These cells then present the antigen(s) to CD4+ lymphocytes and also secrete cytokines such interleukin (IL)-12 and IL-18, thereby inducing the differentiation of TH1 cells in Crohn disease (or, under the control of IL-4, type 2 helper T cells [TH2] in ulcerative colitis). The balance of pro-inflammatory and anti-inflammatory events is also governed by regulatory TH17 and TReg cells, both of which serve to limit immune and inflammatory responses in the GI tract. Transforming growth factor (TGF)β and IL-6 are important cytokines that drive the expansion of the regulatory T cell subsets. The TH1 cells produce a characteristic array of cytokines, including interferon (IFN)γ and TNFα, which in turn activate macrophages. Macrophages positively regulate TH1 cells by secreting additional cytokines, including IFNγ and TNFα. Recruitment of a variety of leukocytes is mediated by activation of resident immune cells including neutrophils. Cell adhesion molecules such as integrins are important in the infiltration of leukocytes and novel biological therapeutic strategies aimed at blocking leukocyte recruitment are effective at reducing inflammation. General immunosuppressants (e.g., glucocorticoids, thioguanine derivatives, methotrexate, and cyclosporine) affect multiple sites of inflammation. More site-specific intervention involves intestinal bacteria (antibiotics, prebiotics, and probiotics) and therapy directed at TNFα or IL-12. (From Brunton LL, Chabner BA, Knollmann RC. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 12th ed. www.accessmedicine.com. Copyright © The McGraw-Hill Companies, Inc. All rights reserved.) Source: GASTROINTESTINAL DISORDERS, The Color Atlas of Physical Therapy Citation: Shamus E. The Color Atlas of Physical Therapy; 2015 Available at: http://accessphysiotherapy.mhmedical.com/DownloadImage.aspx?image=/data/books/1491/p9780071813518-ch041_f002.png&sec=90317035&BookID=1491&ChapterSecID=90316358&imagename= Accessed: October 31, 2017 Copyright © 2017 McGraw-Hill Education. All rights reserved