Ulcerative colitis and cytokines: a literature review





Inflammatory Bowel Disease; Ulcerative Colitis; Cytokines.


Inflammatory Bowel Diseases (IBD) generally affect young individuals, have a global incidence, representing an important public health problem today. Ulcerative colitis is the most common inflammatory bowel disease, characterized by chronic and diffuse inflammation of the intestinal mucosa, often limited to the colon, presenting as main symptoms abdominal pain and mucosanguinolent diarrhea, substantially compromising the quality of life of the individuals affected by it. Its etiology has not yet been fully clarified, however it has been established that a trigger still unknown triggers, in genetically predisposed individuals, an aberrant immune response that culminates in inflammatory processes. The primary pathophysiological elements that guide the beginning, evolution and, ultimately, resolution of IBDs are the responses of the cytokines that characterize them. The first level of cytokine responses is governed by the differentiation patterns of T cells characteristic of each disease. The aim of this study was to conduct a literature review to gather evidence on the profile of cytokines characteristic of ulcerative colitis. The study was carried out through a literature review, with the survey of scientific evidence in the databases Pub Med, Science Direct and Scopus. Ulcerative colitis classically presented as an inflammatory disease mediated by Th2 cells, which has as characteristic cytokines IL 4, IL 5, IL 13, IL 21 and IL 25, however recent evidence has recognized the existence of significant accommodation between cell activation Th2 and Th1 (IFN γ, IL 2 and TNF α) and the auxiliary participation of Th9, Th17 and Th22 cells and regulatory T cells.

Author Biographies

Regina Márcia Soares Cavalcante, Universidade Federal do Piauí


Graduada em Nutrição/UFPI; Especialista em Saúde Pública/UFPI/; Mestre em Ciências e Saúde/PPCS/UFPI; Doutoranda do Programa de Pós-Graduação em Alimentos e Nutrição-PPGAN/UFPI;Professora do Curso de Nutrição da UFPI












Mayara Storel Beserra de Moura, Universidade Federal do Piauí

Graduada em Nutrição-UFPI;Mestre em Ciencias e Saúde-UFPI; Doutoranda do Programa de Pós-Graduação em Alimentos e Nutrição -PPGAN/UFPI

Débora Cavalcante Braz , Universidade Federal do Piauí

Graduada em Farmácia pela Universidade Federal do Piauí-UFPI; Mestre em Farmacologia -UFPI, Doutora pela Rede Norte Nordeste de Biotecnologia (RENORBIO) e  Professora do Curso de Farmácia -UFPI.

Nadir do Nascimento Nogueira, Universidade Federal do Piauí

Graduada em Nutrição-UFPI;Mestre e Doutora em Ciência dos Alimentos -USP; Professora Titular do Curso de Nutrição-UFPI e Vice-Reitora-UFPI.


Ahluwalia, B., Moraes, L., Magnusson, M. K., & Öhman, L. (2018). Immunopathogenesis of inflammatory bowel disease and mechanisms of biological therapies. Scandinavian journal of gastroenterology, 53(4), 379–389. https://doi.org/10.1080/00365521.2018.1447597

Akram, W., Garud, N., & Joshi, R. (2019). Role of inulin as prebiotics on inflammatory bowel disease. Drug discoveries & therapeutics, 13(1), 1–8. https://doi.org/10.5582/ddt.2019.01000

Alexander, W. S., & Hilton, D. J. (2004). The role of suppressors of cytokine signaling (SOCS) proteins in regulation of the immune response. Annual review of immunology, 22, 503–529. https://doi.org/10.1146/annurev.immunol.22.091003.090312

Ananthakrishnan, A. N., Khalili, H., Konijeti, G. G., Higuchi, L. M., de Silva, P., Fuchs, C. S., Willett, W. C., Richter, J. M., & Chan, A. T. (2014). Long-term intake of dietary fat and risk of ulcerative colitis and Crohn's disease. Gut, 63(5), 776–784. https://doi.org/10.1136/gutjnl-2013-305304

Ananthakrishnan, A. N., Khalili, H., Song, M., Higuchi, L. M., Richter, J. M., & Chan, A. T. (2015). Zinc intake and risk of Crohn’s disease and ulcerative colitis: a prospective cohort study. International journal of epidemiology, 44(6), 1995–2005. https://doi.org/10.1093/ije/dyv301

Atreya, R., & Neurath, M. F. (2005). Involvement of IL-6 in the pathogenesis of inflammatory bowel disease and colon cancer. Clinical reviews in allergy & immunology, 28(3), 187–196. https://doi.org/10.1385/CRIAI:28:3:187

Baumgart, D. C., & Sandborn, W. J. (2007). Inflammatory bowel disease: clinical aspects and established and evolving therapies. Lancet (London, England), 369(9573), 1641–1657. https://doi.org/10.1016/S0140-6736(07)60751-X

Becker, C., Fantini, M. C., Schramm, C., Lehr, H. A., Wirtz, S., Nikolaev, A., Burg, J., Strand, S., Kiesslich, R., Huber, S., Ito, H., Nishimoto, N., Yoshizaki, K., Kishimoto, T., Galle, P. R., Blessing, M., Rose-John, S., & Neurath, M. F. (2004). TGF-beta suppresses tumor progression in colon cancer by inhibition of IL-6 trans-signaling. Immunity, 21(4), 491–501. https://doi.org/10.1016/j.immuni.2004.07.020

Bernardo, David. (2013). Human intestinal dendritic cells as controllers of mucosal immunity. Revista Española de Enfermedades Digestivas, 105(5), 279-290. https://dx.doi.org/10.4321/S1130-01082013000500006

Bernstein, C. N., & Forbes, J. D. (2017). Gut Microbiome in Inflammatory Bowel Disease and Other Chronic Immune-Mediated Inflammatory Diseases. Inflammatory intestinal diseases, 2(2), 116–123. https://doi.org/10.1159/000481401

Bernstein, C. N., Fried, M., Krabshuis, J. H., Cohen, H., Eliakim, R., Fedail, S., Gearry, R., Goh, K. L., Hamid, S., Khan, A. G., LeMair, A. W., Malfertheiner, Ouyang, Q., Rey, J. F., Sood, A., Steinwurz, F., Thomsen, O. O., Thomson, A., & Watermeyer, G. (2010). World Gastroenterology Organization Practice Guidelines for the diagnosis and management of IBD in 2010. Inflammatory bowel diseases, 16(1), 112–124. https://doi.org/10.1002/ibd.21048

Biancheri, P., Di Sabatino,A., Corazza, G.R. & MacDonald , T.T.(2013) Proteases and the intestinal barrier. Cell Tissue Res. 351:. 269-280.

Boyman, O., & Sprent, J. (2012). The role of interleukin-2 during homeostasis and activation of the immune system. Nature reviews. Immunology, 12(3), 180–190. https://doi.org/10.1038/nri3156

Brenchley, J. M., & Douek, D. C. (2012). Microbial translocation across the GI tract. Annual review of immunology, 30, 149–173. https://doi.org/10.1146/annurev-immunol-020711-075001

Brombacher, F. (2000). The role of interleukin-13 in infectious diseases and allergy. BioEssays, 22(7), 646–656. doi:10.1002/1521-1878(200007)22:7<646::aid-bies7>3.0.co;2-9

Bull, M. J., & Plummer, N. T. (2014). Part 1: The Human Gut Microbiome in Health and Disease. Integrative medicine (Encinitas, Calif.), 13(6), 17–22.

Burisch, J., & Munkholm, P. (2015). The epidemiology of inflammatory bowel disease. Scandinavian journal of gastroenterology, 50(8), 942–951. https://doi.org/10.3109/00365521.2015.1014407

Calabrese, E., Yanai, H., Shuster, D., Rubin, D. T., & Hanauer, S. B. (2012). Low-dose smoking resumption in ex-smokers with refractory ulcerative colitis. Journal of Crohn's & colitis, 6(7), 756–762. https://doi.org/10.1016/j.crohns.2011.12.010

Cavalcante, R.M.S., Lima, M.M., Parente, J.M.L. & Nogueira, N.N. (2019). O aumento das doenças inflamatórias in testinais no brasil: uma breve reflexão . Revista Nutrição em Pauta, 27(158): 5-10.

Castellanos, J. G., & Longman, R. S. (2019). The balance of power: innate lymphoid cells in tissue inflammation and repair. The Journal of clinical investigation, 129(7), 2640–2650. https://doi.org/10.1172/JCI124617

Caza, T., & Landas, S. (2015). Functional and Phenotypic Plasticity of CD4(+) T Cell Subsets. BioMed research international, 2015, 521957. https://doi.org/10.1155/2015/521957

Chassaing, B., & Gewirtz, A. T. (2014). Pathobiont hypnotises enterocytes to promote tumour development. Gut, 63(12), 1837–1838. https://doi.org/10.1136/gutjnl-2014-306890

Chua, H. H., Chou, H. C., Tung, Y. L., Chiang, B. L., Liao, C. C., Liu, H. H., & Ni, Y. H. (2018). Intestinal Dysbiosis Featuring Abundance of Ruminococcus gnavus Associates With Allergic Diseases in Infants. Gastroenterology, 154(1), 154–167. https://doi.org/10.1053/j.gastro.2017.09.006

Cleynen, I., & Vermeire, S. (2015). The genetic architecture of inflammatory bowel disease: past, present and future. Current opinion in gastroenterology, 31(6), 456–463. https://doi.org/10.1097/MOG.0000000000000215

Cosnes J. (2016). Smoking and Diet: Impact on Disease Course?. Digestive diseases (Basel, Switzerland), 34(1-2), 72–77. https://doi.org/10.1159/000442930

Danese, S., & Fiocchi, C. (2011). Ulcerative colitis. The New England journal of medicine, 365(18), 1713–1725. https://doi.org/10.1056/NEJMra1102942

David, L. A., Maurice, C. F., Carmody, R. N., Gootenberg, D. B., Button, J. E., Wolfe, B. E., Ling, A. V., Devlin, A. S., Varma, Y., Fischbach, M. A., Biddinger, S. B., Dutton, R. J., & Turnbaugh, P. J. (2014). Diet rapidly and reproducibly alters the human gut microbiome. Nature, 505(7484), 559–563. https://doi.org/10.1038/nature12820

Davies, L. C., Jenkins, S. J., Allen, J. E., & Taylor, P. R. (2013). Tissue-resident macrophages. Nature immunology, 14(10), 986–995. https://doi.org/10.1038/ni.2705

DeGruttola, A. K., Low, D., Mizoguchi, A., & Mizoguchi, E. (2016). Current Understanding of Dysbiosis in Disease in Human and Animal Models. Inflammatory bowel diseases, 22(5), 1137–1150. https://doi.org/10.1097/MIB.0000000000000750

Diehl, G. E., Longman, R. S., Zhang, J. X., Breart, B., Galan, C., Cuesta, A., Schwab, S. R., & Littman, D. R. (2013). Microbiota restricts trafficking of bacteria to mesenteric lymph nodes by CX(3)CR1(hi) cells. Nature, 494(7435), 116–120. https://doi.org/10.1038/nature11809

Donath, M. Y., & Shoelson, S. E. (2011). Type 2 diabetes as an inflammatory disease. Nature reviews. Immunology, 11(2), 98–107. https://doi.org/10.1038/nri2925

Dudakov, J. A., Hanash, A. M., & van den Brink, M. R. (2015). Interleukin-22: immunobiology and pathology. Annual review of immunology, 33, 747–785. https://doi.org/10.1146/annurev-immunol-032414-112123

Eckburg, P. B., Bik, E. M., Bernstein, C. N., Purdom, E., Dethlefsen, L., Sargent, M., Gill, S. R., Nelson, K. E., & Relman, D. A. (2005). Diversity of the human intestinal microbial flora. Science (New York, N.Y.), 308(5728), 1635–1638. https://doi.org/10.1126/science.1110591

Forbes, A., Escher, J., Hébuterne, X., Kłęk, S., Krznaric, Z., Schneider, S., Shamir, R., Stardelova, K., Wierdsma, N., Wiskin, A. E., & Bischoff, S. C. (2017). ESPEN guideline: Clinical nutrition in inflammatory bowel disease. Clinical nutrition (Edinburgh, Scotland), 36(2), 321–347. https://doi.org/10.1016/j.clnu.2016.12.027

Francesconi, W. Sánchez-Alavez, M., Berton, F., Alboni, S., Benatti,C., Mori, S., Nguyen,W., Zorrilla, E., Moroncini, G., Tascedda, F. & Conti, B. (2016) The Proinflammatory Cytokine Interleukin 18 Regulates Feeding by Acting on the Bed Nucleus of the Stria Terminalis Journal of Neuroscience . 36 (18): 5170-5180.

Fumery, M., Singh, S., Dulai, P. S., Gower-Rousseau, C., Peyrin-Biroulet, L., & Sandborn, W. J. (2018). Natural History of Adult Ulcerative Colitis in Population-based Cohorts: A Systematic Review. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 16(3), 343–356.e3. https://doi.org/10.1016/j.cgh.2017.06.016

Fuss, I. J., Heller, F., Boirivant, M., Leon, F., Yoshida, M., Fichtner-Feigl, S., Yang, Z., Exley, M., Kitani, A., Blumberg, R. S., Mannon, P., & Strober, W. (2004). Nonclassical CD1d-restricted NK T cells that produce IL-13 characterize an atypical Th2 response in ulcerative colitis. The Journal of clinical investigation, 113(10), 1490–1497. https://doi.org/10.1172/JCI19836

Gasparini, R. G., Sassaki, L. Y., & Saad-Hossne, R. (2018). Inflammatory bowel disease epidemiology in São Paulo State, Brazil. Clinical and experimental gastroenterology, 11, 423–429. https://doi.org/10.2147/CEG.S176583

Geremia, A., Biancheri, P., Allan, P., Corazza, G. R., & Di Sabatino, A. (2014). Innate and adaptive immunity in inflammatory bowel disease. Autoimmunity reviews, 13(1), 3–10. https://doi.org/10.1016/j.autrev.2013.06.004

Glocker, E. O., Kotlarz, D., Boztug, K., Gertz, E. M., Schäffer, A. A., Noyan, F., Perro, M., Diestelhorst, J., Allroth, A., Murugan, D., Hätscher, N., Pfeifer, D., Sykora, K. W., Sauer, M., Kreipe, H., Lacher, M., Nustede, R., Woellner, C., Baumann, U., Salzer, U., … Klein, C. (2009). Inflammatory bowel disease and mutations affecting the interleukin-10 receptor. The New England journal of medicine, 361(21), 2033–2045. https://doi.org/10.1056/NEJMoa0907206

Gradel, K. O., Nielsen, H. L., Schønheyder, H. C., Ejlertsen, T., Kristensen, B., & Nielsen, H. (2009). Increased short- and long-term risk of inflammatory bowel disease after salmonella or campylobacter gastroenteritis. Gastroenterology, 137(2), 495–501. https://doi.org/10.1053/j.gastro.2009.04.001

Greuter, T., & Vavricka, S. R. (2019). Extraintestinal manifestations in inflammatory bowel disease - epidemiology, genetics, and pathogenesis. Expert review of gastroenterology & hepatology, 13(4), 307–317. https://doi.org/10.1080/17474124.2019.1574569

Guo, L., Hu-Li, J., & Paul, W. E. (2005). Probabilistic regulation of IL-4 production. Journal of clinical immunology, 25(6), 573–581. https://doi.org/10.1007/s10875-005-8218-5

Harley, I. T., & Karp, C. L. (2012). Obesity and the gut microbiome: Striving for causality. Molecular metabolism, 1(1-2), 21–31. https://doi.org/10.1016/j.molmet.2012.07.002

Harmsen, H. J., & de Goffau, M. C. (2016). The Human Gut Microbiota. Advances in experimental medicine and biology, 902, 95–108. https://doi.org/10.1007/978-3-319-31248-4_7

Hart, A. L., Al-Hassi, H. O., Rigby, R. J., Bell, S. J., Emmanuel, A. V., Knight, S. C., Kamm, M. A., & Stagg, A. J. (2005). Characteristics of intestinal dendritic cells in inflammatory bowel diseases. Gastroenterology, 129(1), 50–65. https://doi.org/10.1053/j.gastro.2005.05.013

Heller, F., Florian, P., Bojarski, C., Richter, J., Christ, M., Hillenbrand, B., Mankertz, J., Gitter, A. H., Bürgel, N., Fromm, M., Zeitz, M., Fuss, I., Strober, W., & Schulzke, J. D. (2005). Interleukin-13 is the key effector Th2 cytokine in ulcerative colitis that affects epithelial tight junctions, apoptosis, and cell restitution. Gastroenterology, 129(2), 550–564. https://doi.org/10.1016/j.gastro.2005.05.002

Heller, F., Fromm, A., Gitter, A. H., Mankertz, J., & Schulzke, J. D. (2008). Epithelial apoptosis is a prominent feature of the epithelial barrier disturbance in intestinal inflammation: effect of pro-inflammatory interleukin-13 on epithelial cell function. Mucosal immunology, 1 Suppl 1, S58–S61. https://doi.org/10.1038/mi.2008.46

Hershey G. K. (2003). IL-13 receptors and signaling pathways: an evolving web. The Journal of allergy and clinical immunology, 111(4), 677–691. https://doi.org/10.1067/mai.2003.1333

Hevia, A., Delgado, S., Sánchez, B., & Margolles, A. (2015). Molecular Players Involved in the Interaction Between Beneficial Bacteria and the Immune System. Frontiers in microbiology, 6, 1285. https://doi.org/10.3389/fmicb.2015.01285

Hou, J. K., Abraham, B., & El-Serag, H. (2011). Dietary intake and risk of developing inflammatory bowel disease: a systematic review of the literature. The American journal of gastroenterology, 106(4), 563–573. https://doi.org/10.1038/ajg.2011.44

Iannitti, T., & Palmieri, B. (2010). Therapeutical use of probiotic formulations in clinical practice. Clinical nutrition (Edinburgh, Scotland), 29(6), 701–725. https://doi.org/10.1016/j.clnu.2010.05.004

Kakar, S.Cytokines evolution: Role in various diseases,Current Medicine Research and Practice, (2015).5( 4):176-182,https://doi.org/10.1016/j.cmrp.2015.07.002

Khor, B., Gardet, A., & Xavier, R. J. (2011). Genetics and pathogenesis of inflammatory bowel disease. Nature, 474(7351), 307–317. https://doi.org/10.1038/nature10209.

Kimura, A., & Kishimoto, T. (2010). IL-6: regulator of Treg/Th17 balance. European journal of immunology, 40(7), 1830–1835. https://doi.org/10.1002/eji.201040391

Kmieć, Z., Cyman, M., & Ślebioda, T. J. (2017). Cells of the innate and adaptive immunity and their interactions in inflammatory bowel disease. Advances in medical sciences, 62(1), 1–16. https://doi.org/10.1016/j.advms.2016.09.001

Knight-Sepulveda, K., Kais, S., Santaolalla, R., & Abreu, M. T. (2015). Diet and Inflammatory Bowel Disease. Gastroenterology & hepatology, 11(8), 511–520.

Kostic, A. D., Xavier, R. J., & Gevers, D. (2014). The microbiome in inflammatory bowel disease: current status and the future ahead. Gastroenterology, 146(6), 1489–1499. https://doi.org/10.1053/j.gastro.2014.02.009

Kronman, M. P., Zaoutis, T. E., Haynes, K., Feng, R., & Coffin, S. E. (2012). Antibiotic exposure and IBD development among children: a population-based cohort study. Pediatrics, 130(4), e794–e803. https://doi.org/10.1542/peds.2011-3886

Kuhn, K. A., Schulz, H. M., Regner, E. H., Severs, E. L., Hendrickson, J. D., Mehta, G., Whitney, A. K., Ir, D., Ohri, N., Robertson, C. E., Frank, D. N., Campbell, E. L., & Colgan, S. P. (2018). Bacteroidales recruit IL-6-producing intraepithelial lymphocytes in the colon to promote barrier integrity. Mucosal immunology, 11(2), 357–368. https://doi.org/10.1038/mi.2017.55

Lee, T. C., Huang, Y. C., Lu, Y. Z., Yeh, Y. C., & Yu, L. C. (2018). Hypoxia-induced intestinal barrier changes in balloon-assisted enteroscopy. The Journal of physiology, 596(15), 3411–3424. https://doi.org/10.1113/JP275277

Lepage, P., Leclerc, M. C., Joossens, M., Mondot, S., Blottière, H. M., Raes, J., Ehrlich, D., & Doré, J. (2013). A metagenomic insight into our gut's microbiome. Gut, 62(1), 146–158. https://doi.org/10.1136/gutjnl-2011-301805

Leppkes M, Ganslmayer M, Strauss R, Neurath MF (2015) Toxic megacolon. Med Klin Intensivmed Notfmed 110(7):500–505

Lima Martins, A., Volpato, R. A., & Zago-Gomes, M. (2018). The prevalence and phenotype in Brazilian patients with inflammatory bowel disease. BMC gastroenterology, 18(1), 87. https://doi.org/10.1186/s12876-018-0822-y

Lin, L., & Zhang, J. (2017). Role of intestinal microbiota and metabolites on gut homeostasis and human diseases. BMC immunology, 18(1), 2. https://doi.org/10.1186/s12865-016-0187-3

Lindemans, C. A., Calafiore, M., Mertelsmann, A. M., O'Connor, M. H., Dudakov, J. A., Jenq, R. R., Velardi, E., Young, L. F., Smith, O. M., Lawrence, G., Ivanov, J. A., Fu, Y. Y., Takashima, S., Hua, G., Martin, M. L., O'Rourke, K. P., Lo, Y. H., Mokry, M., Romera-Hernandez, M., Cupedo, T., … Hanash, A. M. (2015). Interleukin-22 promotes intestinal-stem-cell-mediated epithelial regeneration. Nature, 528(7583), 560–564. https://doi.org/10.1038/nature16460

Loftus, E.V.(2014) Epidemiology of Inflammatory Bowel Disease In: GI Epidemiology: Diseases and Clinical Methodology: 2th Ed. Wiley Blackwell.p.273-284.

Lu, C., Zhao, X., Lai, M.A., Lopez-Yglesias, A.H., Quarles, E.K., Lo, C. & Smith, K.D. (2016) Commensal E. coli induced colonization resistance against mucosal Salmonella infection. Am Assoc Immnol. 196(Supp.1):.66–71.

Lunney, P. C., Kariyawasam, V. C., Wang, R. R., Middleton, K. L., Huang, T., Selinger, C. P., Andrews, J. M., Katelaris, P. H., & Leong, R. W. (2015). Smoking prevalence and its influence on disease course and surgery in Crohn's disease and ulcerative colitis. Alimentary pharmacology & therapeutics, 42(1), 61–70. https://doi.org/10.1111/apt.13239

Lynch, S. V., & Pedersen, O. (2016). The Human Intestinal Microbiome in Health and Disease. The New England journal of medicine, 375(24), 2369–2379. https://doi.org/10.1056/NEJMra1600266

Ma, A., Koka, R., & Burkett, P. (2006). Diverse functions of IL-2, IL-15, and IL-7 in lymphoid homeostasis. Annual review of immunology, 24, 657–679. https://doi.org/10.1146/annurev.immunol.24.021605.090727

Mai, V., & Draganov, P. V. (2009). Recent advances and remaining gaps in our knowledge of associations between gut microbiota and human health. World journal of gastroenterology, 15(1), 81–85. https://doi.org/10.3748/wjg.15.81

McGovern, D. P., Kugathasan, S., & Cho, J. H. (2015). Genetics of Inflammatory Bowel Diseases. Gastroenterology, 149(5), 1163–1176.e2. https://doi.org/10.1053/j.gastro.2015.08.001

McIlroy, J., Ianiro, G., Mukhopadhya, I., Hansen, R., & Hold, G. L. (2018). Review article: the gut microbiome in inflammatory bowel disease-avenues for microbial management. Alimentary pharmacology & therapeutics, 47(1), 26–42. https://doi.org/10.1111/apt.14384

Miyoshi, J. & Chang, E.B.(2017). The gut microbiota and inflammatory bowel diseases. Transl Res. 179:38–48.

Moller, F. T., Andersen, V., Wohlfahrt, J., & Jess, T. (2015). Familial risk of inflammatory bowel disease: a population-based cohort study 1977-2011. The American journal of gastroenterology, 110(4), 564–571. https://doi.org/10.1038/ajg.2015.50

Monteleone, G., Caruso, R.; Pallone, F. (2013). Targets for new immunomodulation strategies in inflammatory bowel disease. Autoimmunity reviews. Autoimmun. 13: 11–1413.

Murray, P. J., Allen, J. E., Biswas, S. K., Fisher, E. A., Gilroy, D. W., Goerdt, S., Gordon, S., Hamilton, J. A., Ivashkiv, L. B., Lawrence, T., Locati, M., Mantovani, A., Martinez, F. O., Mege, J. L., Mosser, D. M., Natoli, G., Saeij, J. P., Schultze, J. L., Shirey, K. A., Sica, A., … Wynn, T. A. (2014). Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity, 41(1), 14–20. https://doi.org/10.1016/j.immuni.2014.06.008

Murphy, K., Weaver, C. Janeway’s immunobiology. 9th ed. Garland Science; 2017.

Neufert, C., Becker, C., Türeci, Ö., Waldner, M. J., Backert, I., Floh, K., Atreya, I., Leppkes, M., Jefremow, A., Vieth, M., Schneider-Stock, R., Klinger, P., Greten, F. R., Threadgill, D. W., Sahin, U., & Neurath, M. F. (2013). Tumor fibroblast-derived epiregulin promotes growth of colitis-associated neoplasms through ERK. The Journal of clinical investigation, 123(4), 1428–1443. https://doi.org/10.1172/JCI63748

Neurath, M. F., & Finotto, S. (2011). IL-6 signaling in autoimmunity, chronic inflammation and inflammation-associated cancer. Cytokine & growth factor reviews, 22(2), 83–89. https://doi.org/10.1016/j.cytogfr.2011.02.003

Neurath M. F. (2014). Cytokines in inflammatory bowel disease. Nature reviews. Immunology, 14(5), 329–342. https://doi.org/10.1038/nri3661

Ni, J., Wu, G. D., Albenberg, L., & Tomov, V. T. (2017). Gut microbiota and IBD: causation or correlation?. Nature reviews. Gastroenterology & hepatology, 14(10), 573–584. https://doi.org/10.1038/nrgastro.2017.88

Niess, J. H., Brand, S., Gu, X., Landsman, L., Jung, S., McCormick, B. A., Vyas, J. M., Boes, M., Ploegh, H. L., Fox, J. G., Littman, D. R., & Reinecker, H. C. (2005). CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance. Science (New York, N.Y.), 307(5707), 254–258. https://doi.org/10.1126/science.1102901

Ng, S. C., Bernstein, C. N., Vatn, M. H., Lakatos, P. L., Loftus, E. V., Jr, Tysk, C., O'Morain, C., Moum, B., Colombel, J. F., & Epidemiology and Natural History Task Force of the International Organization of Inflammatory Bowel Disease (IOIBD) (2013). Geographical variability and environmental risk factors in inflammatory bowel disease. Gut, 62(4), 630–649. https://doi.org/10.1136/gutjnl-2012-303661

Ng, S.C., Shi, H.Y., HAMIDI, N.; UNDERWOOD, F.E.; TANG ,W.; BENCHIMOL, E.I.; PANACCIONE, R.; GHOSH,S.; WU, J.C.Y.; CHAN, F.K.L.; SUNG, J.J.Y.; KAPLAN,G.G.; Worldwide incidence and prevalence of inflammatory bowel disease in the 21stcentury: a systematic review of population-based studies, Lancet v 390, nº 10114 p 2769–2778, 2018.

O'Keeffe, M., Mok, W. H., & Radford, K. J. (2015). Human dendritic cell subsets and function in health and disease. Cellular and molecular life sciences : CMLS, 72(22), 4309–4325. https://doi.org/10.1007/s00018-015-2005-0

Oliveira, F. M., Emerick, A. P. C. & Soares, E. G.(2010) Aspectos epidemiológicos das doenças intestinais inflamatórias na macrorregião de saúde leste do Estado de Minas Gerais. Cien. Saude Colet. 15(1):1031-1037.

Ordás, I., Eckmann, L., Talamini, M., Baumgart, D. C., & Sandborn, W. J. (2012). Ulcerative colitis. Lancet (London, England), 380(9853), 1606–1619. https://doi.org/10.1016/S0140-6736(12)60150-0

Parente, J. M., Coy, C. S., Campelo, V., Parente, M. P., Costa, L. A., da Silva, R. M., Stephan, C., & Zeitune, J. M. (2015). Inflammatory bowel disease in an underdeveloped region of Northeastern Brazil. World journal of gastroenterology, 21(4), 1197–1206. https://doi.org/10.3748/wjg.v21.i4.1197

Peterson, L. W., & Artis, D. (2014). Intestinal epithelial cells: regulators of barrier function and immune homeostasis. Nature reviews. Immunology, 14(3), 141–153. https://doi.org/10.1038/nri3608

Peyrin-Biroulet L, Sandborn W, Sands BE, et al. Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE): Determining Therapeutic Goals for Treat-to-Target. Am J Gastroenterol. 2015;110(9):1324-1338. doi:10.1038/ajg.2015.233

Prorok-Hamon, M., Friswell, M. K., Alswied, A., Roberts, C. L., Song, F., Flanagan, P. K., Knight, P., Codling, C., Marchesi, J. R., Winstanley, C., Hall, N., Rhodes, J. M., & Campbell, B. J. (2014). Colonic mucosa-associated diffusely adherent afaC+ Escherichia coli expressing lpfA and pks are increased in inflammatory bowel disease and colon cancer. Gut, 63(5), 761–770. https://doi.org/10.1136/gutjnl-2013-304739

Quigley, E.M. (2011). Gut microbiota and the role of probiotics in therapy. Current opinion in pharmacology. 11(6): 593-603. 10.1016/j.coph.2011.09.010.

Raphael, I., Nalawade, S., Eagar, T. N., & Forsthuber, T. G. (2015). T cell subsets and their signature cytokines in autoimmune and inflammatory diseases. Cytokine, 74(1), 5–17. https://doi.org/10.1016/j.cyto.2014.09.011

Reuter, B. K., & Pizarro, T. T. (2009). Mechanisms of tight junction dysregulation in the SAMP1/YitFc model of Crohn's disease-like ileitis. Annals of the New York Academy of Sciences, 1165, 301–307. https://doi.org/10.1111/j.1749-6632.2009.04035.x

Sato, T. A., Widmer, M. B., Finkelman, F. D., Madani, H., Jacobs, C. A., Grabstein, K. H., & Maliszewski, C. R. (1993). Recombinant soluble murine IL-4 receptor can inhibit or enhance IgE responses in vivo. Journal of immunology (Baltimore, Md. : 1950), 150(7), 2717–2723.

Satoh-Takayama, N., Serafini, N., Verrier, T., Rekiki, A., Renauld, J. C., Frankel, G., & Di Santo, J. P. (2014). The chemokine receptor CXCR6 controls the functional topography of interleukin-22 producing intestinal innate lymphoid cells. Immunity, 41(5), 776–788. https://doi.org/10.1016/j.immuni.2014.10.007

Schmitt, E., Klein, M., & Bopp, T. (2014). Th9 cells, new players in adaptive immunity. Trends in immunology, 35(2), 61–68. https://doi.org/10.1016/j.it.2013.10.004

Schmitt, N., & Ueno, H. (2015). Regulation of human helper T cell subset differentiation by cytokines. Current opinion in immunology, 34, 130–136. https://doi.org/10.1016/j.coi.2015.03.007

Sender, R., Fuchs, S., & Milo, R. (2016). Are We Really Vastly Outnumbered? Revisiting the Ratio of Bacterial to Host Cells in Humans. Cell, 164(3), 337–340. https://doi.org/10.1016/j.cell.2016.01.013

Shaw, S. Y., Blanchard, J. F., & Bernstein, C. N. (2010). Association between the use of antibiotics in the first year of life and pediatric inflammatory bowel disease. The American journal of gastroenterology, 105(12), 2687–2692. https://doi.org/10.1038/ajg.2010.398

Shreiner, A. B., Kao, J. Y., & Young, V. B. (2015). The gut microbiome in health and in disease. Current opinion in gastroenterology, 31(1), 69–75. https://doi.org/10.1097/MOG.0000000000000139

Singh, R. P., Hasan, S., Sharma, S., Nagra, S., Yamaguchi, D. T., Wong, D. T., Hahn, B. H., & Hossain, A. (2014). Th17 cells in inflammation and autoimmunity. Autoimmunity reviews, 13(12), 1174–1181. https://doi.org/10.1016/j.autrev.2014.08.019

Sobieszczańska, B. A., Duda-Madej, A. B., Turniak, M. B., Franiczek, R., Kasprzykowska, U., Duda, A. K., Rzeszutko, M., & Iwańczak, B. (2012). Invasive properties, adhesion patterns and phylogroup profiles among Escherichia coli strains isolated from children with inflammatory bowel disease. Advances in clinical and experimental medicine : official organ Wroclaw Medical University, 21(5), 591–599.

Sonnenberg, G. F., & Artis, D. (2019). Novel connections and precision approaches. Nature reviews. Immunology, 19(2), 75–76. https://doi.org/10.1038/s41577-018-0114-3

Souza, José Roberto Matos, Oliveira, Romulo Tadeu, Blotta, Maria Heloisa S. L., & Coelho, Otávio Rizzi. (2008). Serum levels of interleukin-6 (Il-6), interleukin-18 (Il-18) and C-reactive protein (CRP) in patients with type-2 diabetes and acute coronary syndrome without ST-segment elevation. Arquivos Brasileiros de Cardiologia, 90(2), 94-99. https://dx.doi.org/10.1590/S0066-782X2008000200004

Stappenbeck, T. S., Rioux, J. D., Mizoguchi, A., Saitoh, T., Huett, A., Darfeuille-Michaud, A., Wileman, T., Mizushima, N., Carding, S., Akira, S., Parkes, M., & Xavier, R. J. (2011). Crohn disease: a current perspective on genetics, autophagy and immunity. Autophagy, 7(4), 355–374. https://doi.org/10.4161/auto.7.2.13074

Strober, W., & Fuss, I. J. (2011). Proinflammatory cytokines in the pathogenesis of inflammatory bowel diseases. Gastroenterology, 140(6), 1756–1767. https://doi.org/10.1053/j.gastro.2011.02.016

Ueno, H., Banchereau, J., & Vinuesa, C. G. (2015). Pathophysiology of T follicular helper cells in humans and mice. Nature immunology, 16(2), 142–152. https://doi.org/10.1038/ni.3054

Ungar, B., & Kopylov, U. (2016). Advances in the development of new biologics in inflammatory bowel disease. Annals of gastroenterology, 29(3), 243–248. https://doi.org/10.20524/aog.2016.0027

Ungaro, R., Mehandru, S., Allen, P. B., Peyrin-Biroulet, L., & Colombel, J. F. (2017). Ulcerative colitis. Lancet (London, England), 389(10080), 1756–1770. https://doi.org/10.1016/S0140-6736(16)32126-2

Van der Heide, F., Dijkstra, A., Weersma, R. K., Albersnagel, F. A., van der Logt, E. M., Faber, K. N., Sluiter, W. J., Kleibeuker, J. H., & Dijkstra, G. (2009). Effects of active and passive smoking on disease course of Crohn's disease and ulcerative colitis. Inflammatory bowel diseases, 15(8), 1199–1207. https://doi.org/10.1002/ibd.20884

Walker, A.W., Ince, J., Duncan, S.H., Webster, L.M., Holtrop, G., Ze, X., Brown, D., Stares, M.D., Scott, P., Bergerat, A. , Louis, P., McIntosh, F., Johnstone, A.M., Lobley, G.E., Parkhill, J., & Flint,H.J . (2011). Dominant and diet-responsive groups of bacteria within the human colonic microbiota.The ISME Journal .5(2):220–230.

Wallace, K. L., Zheng, L. B., Kanazawa, Y., & Shih, D. Q. (2014). Immunopathology of inflammatory bowel disease. World journal of gastroenterology, 20(1), 6–21. https://doi.org/10.3748/wjg.v20.i1.6

Wang, M. H., Fiocchi, C., Ripke, S., Zhu, X., Duerr, R. H., & Achkar, J. P. (2013). A novel approach to detect cumulative genetic effects and genetic interactions in Crohn's disease. Inflammatory bowel diseases, 19(9), 1799–1808. https://doi.org/10.1097/MIB.0b013e31828706a0

Wu, G. D., Chen, J., Hoffmann, C., Bittinger, K., Chen, Y. Y., Keilbaugh, S. A., Bewtra, M., Knights, D., Walters, W. A., Knight, R., Sinha, R., Gilroy, E., Gupta, K., Baldassano, R., Nessel, L., Li, H., Bushman, F. D., & Lewis, J. D. (2011). Linking long-term dietary patterns with gut microbial enterotypes. Science (New York, N.Y.), 334(6052), 105–108. https://doi.org/10.1126/science.1208344

Yu, L.C., Wei, S., & Ni, Y. (2017). Interplay between the gut microbiota and epithelial innate signaling in colitis-associated colon carcinogenesis. Cancer Res Frontiers. 3(1):1–28.

Yu, L. C., Wang, J. T., Wei, S. C., & Ni, Y. H. (2012). Host-microbial interactions and regulation of intestinal epithelial barrier function: From physiology to pathology. World journal of gastrointestinal pathophysiology, 3(1), 27–43. https://doi.org/10.4291/wjgp.v3.i1.27

Zhang, Y. Z., & Li, Y. Y. (2014). Inflammatory bowel disease: pathogenesis. World journal of gastroenterology, 20(1), 91–99. https://doi.org/10.3748/wjg.v20.i1.91

Zhu, S., & Qian, Y. (2012). IL-17/IL-17 receptor system in autoimmune disease: mechanisms and therapeutic potential. Clinical science (London, England : 1979), 122(11), 487–511. https://doi.org/10.1042/CS20110496

Zigmond, E., Varol, C., Farache, J., Elmaliah, E., Satpathy, A. T., Friedlander, G., Mack, M., Shpigel, N., Boneca, I. G., Murphy, K. M., Shakhar, G., Halpern, Z., & Jung, S. (2012). Ly6C hi monocytes in the inflamed colon give rise to proinflammatory effector cells and migratory antigen-presenting cells. Immunity, 37(6), 1076–1090. https://doi.org/10.1016/j.immuni.2012.08.026

Zoeten, E.F. & Fuss, I.J.(2017). Cytokines and Inflammatory Bowel Disease.In: Pediatric Inflammatory Bowel Disease pp.31-43.. 10.1007/978-3-319-49215-5_3.



How to Cite

Cavalcante, R. M. S. ., Moura, M. S. B. de, Braz , D. . C., & Nogueira, N. do N. . (2020). Ulcerative colitis and cytokines: a literature review. Research, Society and Development, 9(9), e314997145. https://doi.org/10.33448/rsd-v9i9.7145



Health Sciences