Skip to main content

Inflammatory Diseases of the Gastrointestinal Tract and Pharmacological Treatments

  • Chapter
  • First Online:
Pharmacology of Immunotherapeutic Drugs

Abstract

The human gastrointestinal (GI) tract is critical for the digestion and absorption of food and the elimination of waste products. The absorption of dietary nutrients is facilitated through a physical epithelial barrier consisting of numerous finger-like projections called villi that promote the uptake of nutrients throughout the body. This same epithelial barrier also prevents bacterial invasion, a remarkable accomplishment, considering that trillions of bacteria normally live within the lumen of the gut, reaching densities of up to 1012 organisms per gram in the colon. These normal intestinal flora or microbiota, the composition of which varies from individual to individual, play a pivotal role in the shaping and direction of mucosal immune responses within the GI tract. Mucosal immune responses within the GI tract are tailored toward limiting opportunistic infections caused by commensal bacteria, while protecting the body’s inner surfaces from colonization by pathogens. Perturbations of normal immune homeostasis within the GI tract, either due to infection or injury, defects in barrier function, induction of autoimmune mechanisms, and disruption of commensal bacterial composition, may lead to chronic inflammatory processes, leading to the development of diseases such as inflammatory bowel disease, celiac disease, food allergy and other conditions. In this chapter, we will examine the inflammatory processes and immunotherapeutic drug targets involved in the development of the above diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Suggested Reading

  • Ahnfelt-Rønne I, et al. Clinical evidence supporting the radical scavenger mechanism of 5-aminosalicylic acid. Gastroenterology. 1990;98:1162–9.

    Article  PubMed  Google Scholar 

  • Blander JM, Longman RS, Iliev ID, Sonnenberg GF, Artis D. Regulation of inflammation by microbiota interactions with the host. Nat Immunol. 2017;18:851–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Boyce JA, et al. Guidelines for the diagnosis and management of food allergy in the United States: summary of the NIAID-sponsored expert panel report. J Allergy Clin Immunol. 2010;126:1105–18.

    Article  PubMed  PubMed Central  Google Scholar 

  • Bramuzzo M, Ventura A, Martelossi S, Lazzerini M. Thalidomide for inflammatory bowel disease. Medicine. 2016;95:e4239.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bryce PJ. Balancing tolerance or allergy to food proteins. Trends Immunol. 2016;37:659–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Burks AW, Sampson HA, Plaut M, Lack G, Akdis CA. Treatment for food allergy. J Allergy Clin Immunol. 2018;141:1–9.

    Article  PubMed  Google Scholar 

  • Carter MJ. Guidelines for the management of inflammatory bowel disease in adults. Gut. 2004;53:v1–v16.

    Article  PubMed  PubMed Central  Google Scholar 

  • Chang C, Lin H. Dysbiosis in gastrointestinal disorders. Best Pract Res Clin Gastroenterol. 2016;30:3–15.

    Article  PubMed  Google Scholar 

  • Chehade M, et al. Phenotypic characterization of eosinophilic esophagitis in a large multicenter patient population from the consortium for food allergy research. J Allergy Clin Immunol Pract. 2018;6:1534–44.e1535.

    Article  PubMed  PubMed Central  Google Scholar 

  • DeRoche TC, Xiao SY, Liu X. Histological evaluation in ulcerative colitis. Gastroenterol Rep (Oxf). 2014;2:178–92.

    Article  Google Scholar 

  • Desreumaux P, et al. Safety and efficacy of antigen-specific regulatory T-cell therapy for patients with refractory Crohn’s disease. Gastroenterology. 2012;143:1207–17.e1202.

    Article  CAS  PubMed  Google Scholar 

  • Dotan I. New serologic markers for inflammatory bowel disease diagnosis. Dig Dis. 2010;28:418–23.

    Article  PubMed  Google Scholar 

  • Du Toit G, et al. Randomized trial of peanut consumption in infants at risk for peanut allergy. N Engl J Med. 2015;372:803–13.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Du Toit G, et al. Food allergy: update on prevention and tolerance. J Allergy Clin Immunol. 2018;141:30–40.

    Article  PubMed  CAS  Google Scholar 

  • Feagan BG, et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2013;369:699–710.

    Article  CAS  PubMed  Google Scholar 

  • Fernández-Ramos AA, et al. 6-mercaptopurine promotes energetic failure in proliferating T cells. Oncotarget. 2017;8:43048–60.

    Article  PubMed  PubMed Central  Google Scholar 

  • Freeman HJ. Adult celiac disease and its malignant complications. Gut Liver. 2009;3:237–46.

    Article  PubMed  PubMed Central  Google Scholar 

  • Friedman RM, Contente S. Treatment of hepatitis C infections with interferon: a historical perspective. Hepat Res Treat. 2010;2010:323926.

    PubMed  PubMed Central  Google Scholar 

  • Fuss IJ, Neurath MF, Boirivant M, Fiocchi C, Strober W. Disparate CD4+ lamina propria (LP) lymphokine secretion profiles in inflammatory bowel disease. Shock. 1997;7:130.

    Article  Google Scholar 

  • Gerner RR, Moschen AR, Tilg H. Targeting T and B lymphocytes in inflammatory bowel diseases: lessons from clinical trials. Dig Dis. 2013;31:328–35.

    Article  CAS  PubMed  Google Scholar 

  • Gupta RS, et al. Hygiene factors associated with childhood food allergy and asthma. Allergy Asthma Proc. 2016;37:140–6.

    Article  Google Scholar 

  • Heim MH. Interferons and hepatitis C virus. Swiss Med Wkly. 2012;142:w13586.

    PubMed  Google Scholar 

  • Hendrickson BA, Gokhale R, Cho JH. Clinical aspects and pathophysiology of inflammatory bowel disease. Clin Microbiol Rev. 2002;15:79–94.

    Article  PubMed  PubMed Central  Google Scholar 

  • Hugot J-P, et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease. Nature. 2001;411:599–603.

    Article  CAS  PubMed  Google Scholar 

  • Isaacs A, Lindenmann J. Pillars article: virus interference. I. The interferon. Proc R Soc Lond B Biol Sci. 1957;147:258–67. J Immunol. 2015;195:1911–20.

    Google Scholar 

  • Jabri B, Abadie V. IL-15 functions as a danger signal to regulate tissue-resident T cells and tissue destruction. Nat Rev Immunol. 2015;15:771–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Joyce MA, Tyrrell DL. The cell biology of hepatitis C virus. Microbes Infect. 2010;12:263–71.

    Article  CAS  PubMed  Google Scholar 

  • Kaistha A, Levine J. Inflammatory bowel disease: the classic gastrointestinal autoimmune disease. Curr Probl Pediatr Adolesc Health Care. 2014;44:328–34.

    Article  PubMed  Google Scholar 

  • Kalliolias GD, Ivashkiv LB. TNF biology, pathogenic mechanisms and emerging therapeutic strategies. Nat Rev Rheumatol. 2015;12:49–62.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kamdar TA, et al. Prevalence and characteristics of adult-onset food allergy. J Allergy Clin Immunol Pract. 2015;3:114–5.e111.

    Article  PubMed  Google Scholar 

  • Kaukinen K, Maki M. Coeliac disease in 2013: new insights in dietary-gluten-induced autoimmunity. Nat Rev Gastroenterol Hepatol. 2014;11:80–2.

    Article  PubMed  Google Scholar 

  • Kaukinen K, Lindfors K, Maki M. Advances in the treatment of coeliac disease: an immunopathogenic perspective. Nat Rev Gastroenterol Hepatol. 2014;11:36–44.

    Article  CAS  PubMed  Google Scholar 

  • Kinney SR, et al. Curcumin ingestion inhibits mastocytosis and suppresses intestinal anaphylaxis in a murine model of food allergy. PLoS One. 2015;10:e0132467.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kobayashi T, et al. IL-10 regulates Il12b expression via histone deacetylation: implications for intestinal macrophage homeostasis. J Immunol. 2012;189:1792–9.

    Article  CAS  PubMed  Google Scholar 

  • Koplin JJ, Perrett KP, Sampson HA. Diagnosing peanut allergy with fewer oral food challenges. J Allergy Clin Immunol Pract. 2019;7:375–80.

    Article  PubMed  Google Scholar 

  • Kühn R, Löhler J, Rennick D, Rajewsky K, Müller W. Interleukin-10-deficient mice develop chronic enterocolitis. Cell. 1993;75:263–74.

    Article  PubMed  Google Scholar 

  • Kuja-Halkola R, et al. Heritability of non-HLA genetics in coeliac disease: a population-based study in 107 000 twins. Gut. 2016;65:1793–8.

    Article  PubMed  Google Scholar 

  • Larsen EP, Bayat A, Vyberg M. Small duct autoimmune sclerosing cholangitis and Crohn colitis in a 10-year-old child. A case report and review of the literature. Diagn Pathol. 2012;7:100.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lebwohl B, Green PH, Genta RM. The coeliac stomach: gastritis in patients with coeliac disease. Aliment Pharmacol Ther. 2015;42:180–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lebwohl B, Sanders DS, Green PHR. Coeliac disease. Lancet. 2018;391:70–81.

    Article  PubMed  Google Scholar 

  • Leffler DA, Green PH, Fasano A. Extraintestinal manifestations of coeliac disease. Nat Rev Gastroenterol Hepatol. 2015;12:561–71.

    Article  CAS  PubMed  Google Scholar 

  • Macpherson A, Khoo UY, Forgacs I, Philpott-Howard J, Bjarnason I. Mucosal antibodies in inflammatory bowel disease are directed against intestinal bacteria. Gut. 1996;38:365–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maloy KJ, Powrie F. Intestinal homeostasis and its breakdown in inflammatory bowel disease. Nature. 2011;474:298–306.

    Article  CAS  PubMed  Google Scholar 

  • Mantis NJ, Rol N, Corthésy B. Secretory IgA’s complex roles in immunity and mucosal homeostasis in the gut. Mucosal Immunol. 2011;4:603–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marild K, et al. Antibiotic exposure and the development of coeliac disease: a nationwide case-control study. BMC Gastroenterol. 2013;13:109.

    Article  PubMed  PubMed Central  Google Scholar 

  • Mbodji K, et al. Adjunct therapy of n-3 fatty acids to 5-ASA ameliorates inflammatory score and decreases NF-κB in rats with TNBS-induced colitis. J Nutr Biochem. 2013;24:700–5.

    Article  CAS  PubMed  Google Scholar 

  • Millrine D, Kishimoto T. A brighter side to thalidomide: its potential use in immunological disorders. Trends Mol Med. 2017;23:348–61.

    Article  CAS  PubMed  Google Scholar 

  • Murai M, et al. Interleukin 10 acts on regulatory T cells to maintain expression of the transcription factor Foxp3 and suppressive function in mice with colitis. Nat Immunol. 2009;10:1178–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nagler-Anderson C. Man the barrier! Strategic defences in the intestinal mucosa. Nat Rev Immunol. 2001;1:59–67.

    Article  CAS  PubMed  Google Scholar 

  • Naon H, Mcgilligan K, Reifen R, Sherman P, Sinatra F, Thomas D. Salivary secretory immunoglobulin A in pediatric patients with chronic idiopathic inflammatory bowel disease. Gastroenterology. 1995;108:A884.

    Google Scholar 

  • Neurath MF. Current and emerging therapeutic targets for IBD. Nat Rev Gastroenterol Hepatol. 2017;14:269–78.

    Article  CAS  PubMed  Google Scholar 

  • Nowak-Wegrzyn A, Szajewska H, Lack G. Food allergy and the gut. Nat Rev Gastroenterol Hepatol. 2016;14:241–57.

    Article  PubMed  CAS  Google Scholar 

  • Oakley RH, Cidlowski JA. The biology of the glucocorticoid receptor: new signaling mechanisms in health and disease. J Allergy Clin Immunol. 2013;132:1033–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Odenwald MA, Turner JR. The intestinal epithelial barrier: a therapeutic target? Nat Rev Gastroenterol Hepatol. 2017;14:9–21.

    Article  CAS  PubMed  Google Scholar 

  • Ogura Y, et al. A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease. Nature. 2001;411:603–6.

    Article  CAS  PubMed  Google Scholar 

  • O’Hara AM, Shanahan F. The gut flora as a forgotten organ. EMBO Rep. 2006;7:688–93.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Oyoshi MK, Oettgen HC, Chatila TA, Geha RS, Bryce PJ. Food allergy: insights into etiology, prevention, and treatment provided by murine models. J Allergy Clin Immunol. 2014;133:309–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pamer EG. Immune responses to commensal and environmental microbes. Nat Immunol. 2007;8:1173–8.

    Article  CAS  PubMed  Google Scholar 

  • Parzanese I, et al. Celiac disease: from pathophysiology to treatment. World J Gastrointest Pathophysiol. 2017;8:27–38.

    Article  PubMed  PubMed Central  Google Scholar 

  • Perkin MR, et al. Randomized trial of introduction of allergenic foods in breast-fed infants. N Engl J Med. 2016;374:1733–43.

    Article  CAS  PubMed  Google Scholar 

  • Pestka S. The interferons: 50 years after their discovery, there is much more to learn. J Biol Chem. 2007;282:20047–51.

    Article  CAS  PubMed  Google Scholar 

  • Plevy S, et al. Combined serological, genetic, and inflammatory markers differentiate non-IBD, Crohnʼs disease, and ulcerative colitis patients. Inflamm Bowel Dis. 2013;19:1139–48.

    Article  PubMed  Google Scholar 

  • Polukort SH, et al. IL-10 enhances IgE-mediated mast cell responses and is essential for the development of experimental food allergy in IL-10-deficient mice. J Immunol. 2016;196:4865–76.

    Article  CAS  PubMed  Google Scholar 

  • Prince BT, et al. Regulatory T-cell populations in children are affected by age and food allergy diagnosis. J Allergy Clin Immunol. 2017;140:1194–6.e1116.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Quinton JF, et al. Anti-Saccharomyces cerevisiae mannan antibodies combined with antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease: prevalence and diagnostic role. Gut. 1998;42:788–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rakoff-Nahoum S, Hao L, Medzhitov R. Role of toll-like receptors in spontaneous commensal-dependent colitis. Immunity. 2006;25:319–29.

    Article  CAS  PubMed  Google Scholar 

  • Renz H, et al. Food allergy. Nat Rev Dis Primers. 2018;4:17098.

    Article  PubMed  Google Scholar 

  • Roulis M, et al. Host and microbiota interactions are critical for development of murine Crohn’s-like ileitis. Mucosal Immunol. 2015;9:787–97.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sampson HA. Food allergy: past, present and future. Allergol Int. 2016;65:363–9.

    Article  PubMed  Google Scholar 

  • Sandborn WJ, et al. Vedolizumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med. 2013;369:711–21.

    Article  CAS  PubMed  Google Scholar 

  • See JA, Kaukinen K, Makharia GK, Gibson PR, Murray JA. Practical insights into gluten-free diets. Nat Rev Gastroenterol Hepatol. 2015;12:580–91.

    Article  CAS  PubMed  Google Scholar 

  • Sicherer SH, Sampson HA. Food allergy: a review and update on epidemiology, pathogenesis, diagnosis, prevention, and management. J Allergy Clin Immunol. 2018;141:41–58.

    Article  CAS  PubMed  Google Scholar 

  • Smith PK, Masilamani M, Li XM, Sampson HA. The false alarm hypothesis: food allergy is associated with high dietary advanced glycation end-products and proglycating dietary sugars that mimic alarmins. J Allergy Clin Immunol. 2017;139:429–37.

    Article  CAS  PubMed  Google Scholar 

  • Soler D, et al. The binding specificity and selective antagonism of vedolizumab, an anti-α4β7 integrin therapeutic antibody in development for inflammatory bowel diseases. J Pharmacol Exp Ther. 2009;330:864–75.

    Article  CAS  PubMed  Google Scholar 

  • Sollid LM, Jabri B. Triggers and drivers of autoimmunity: lessons from coeliac disease. Nat Rev Immunol. 2013;13:294–302.

    Article  CAS  PubMed  Google Scholar 

  • Steinbach EC, Plevy SE. The role of macrophages and dendritic cells in the initiation of inflammation in IBD. Inflamm Bowel Dis. 2014;20:166–75.

    Article  PubMed  Google Scholar 

  • Thaiss CA, Zmora N, Levy M, Elinav E. The microbiome and innate immunity. Nature. 2016;535:65–74.

    Article  CAS  PubMed  Google Scholar 

  • Tokuhara D, et al. A comprehensive understanding of the gut mucosal immune system in allergic inflammation. Allergol Int. 2019;68:17–25.

    Article  PubMed  Google Scholar 

  • Tordesillas L, Berin MC, Sampson HA. Immunology of food allergy. Immunity. 2017;47:32–50.

    Article  CAS  PubMed  Google Scholar 

  • Tran-Minh M-L, Sousa P, Maillet M, Allez M, Gornet J-M. Hepatic complications induced by immunosuppressants and biologics in inflammatory bowel disease. World J Hepatol. 2017;9:613–26.

    Article  PubMed  PubMed Central  Google Scholar 

  • van Gils T, Nijeboer P, van Wanrooij RL, Bouma G, Mulder CJ. Mechanisms and management of refractory coeliac disease. Nat Rev Gastroenterol Hepatol. 2015;12:572–9.

    Article  PubMed  CAS  Google Scholar 

  • Verdu EF, Galipeau HJ, Jabri B. Novel players in coeliac disease pathogenesis: role of the gut microbiota. Nat Rev Gastroenterol Hepatol. 2015;12:497–506.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vilcek J. Fifty years of interferon research: aiming at a moving target. Immunity. 2006;25:343–8.

    Article  CAS  PubMed  Google Scholar 

  • Volta U, De Giorgio R. New understanding of gluten sensitivity. Nat Rev Gastroenterol Hepatol. 2012;9:295–9.

    Article  CAS  PubMed  Google Scholar 

  • Vriezinga SL, Schweizer JJ, Koning F, Mearin ML. Coeliac disease and gluten-related disorders in childhood. Nat Rev Gastroenterol Hepatol. 2015;12:527–36.

    Article  CAS  PubMed  Google Scholar 

  • Wang J, Sampson HA. Safety and efficacy of epicutaneous immunotherapy for food allergy. Pediatr Allergy Immunol. 2018;29:341–9.

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y-Z. Inflammatory bowel disease: pathogenesis. World J Gastroenterol. 2014;20:91–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Clinton B. Mathias .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Mathias, C.B., McAleer, J.P., Szollosi, D.E. (2020). Inflammatory Diseases of the Gastrointestinal Tract and Pharmacological Treatments. In: Mathias, C., McAleer, J., Szollosi, D. (eds) Pharmacology of Immunotherapeutic Drugs. Springer, Cham. https://doi.org/10.1007/978-3-030-19922-7_6

Download citation

Publish with us

Policies and ethics