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ISSN (Print): 1381-6128
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Systematic Review Article

Current, New and Future Therapeutic Targets in Inflammatory Bowel Disease: A Systematic Review

Author(s): Niloufar Alimohammadi, Farzad Koosha and Mahmoud Rafeian-Kopaei*

Volume 26, Issue 22, 2020

Page: [2668 - 2675] Pages: 8

DOI: 10.2174/1381612826666200406081920

Price: $65

Abstract

Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic relapsing conditions resulting from immune system activity in a genetically predisposed individual. IBD is based on progressive damage to the inflamed gut tissue. As its pathogenesis remains unknown, recent accumulating data have demonstrated that IBD is a complex and multi-factorial disorder correlated with host luminal factors, which lead to an imbalance between pro- and anti-inflammatory signaling. The growing understanding of the molecular mechanisms responsible for IBD has suggested a wide range of potential therapeutic targets to treat this condition. Some patients do not have a satisfactory response to current therapeutic medications such as antitumor necrosis factor (TNF) agents, or their response decreases over time. As a result, IBD therapeutics have been changed recently, with several new agents being evaluated. The identification of various inflammatory cascades has led to forming the idea to have novel medications developed. Medications targeting Janus kinases (JAK), leukocyte trafficking Interleukin (IL) 12/23, and Sphingosine 1 phosphate (S1P) are among these newly developed medications and highlight the role of microbial-host interaction in inflammation as a safe promising strategy. This systematic review aims to summarize different molecular targeting therapeutics, the most potent candidates for IBD treatment in recent studies.

Keywords: Inflammatory bowel disease, therapy target, Crohn's disease, ulcerative colitis, medicinal plants, intestinal microbiota.

« Previous Next »
[1]
Mak A, Isenberg DA, Lau CS. Global trends, potential mechanisms and early detection of organ damage in SLE. Nat Rev Rheumatol 2013; 9(5): 301-10.
[http://dx.doi.org/10.1038/nrrheum.2012.208] [PMID: 23229448]
[2]
Jönsen A, Bengtsson AA, Hjalte F, Petersson IF, Willim M, Nived O. Total cost and cost predictors in systemic lupus erythematosus - 8-years follow-up of a Swedish inception cohort. Lupus 2015; 24(12): 1248-56.
[http://dx.doi.org/10.1177/0961203315584812] [PMID: 25957301]
[3]
Zhang L, Lu GH, Ye S, Wu B, Shen Y, Li T. Treatment adherence and disease burden of individuals with rheumatic diseases admitted as outpatients to a large rheumatology center in Shanghai, China. Patient Prefer Adherence 2017; 11: 1591-601.
[http://dx.doi.org/10.2147/PPA.S144624] [PMID: 29075106]
[4]
Pons-Estel GJ, Alarcón GS, Scofield L, Reinlib L, Cooper GS. Understanding the epidemiology and progression of systemic lupus erythematosus. Semin Arthritis Rheum 2010; 39(4): 257-68.
[http://dx.doi.org/10.1016/j.semarthrit.2008.10.007] [PMID: 19136143]
[5]
Charles PJ. Defective waste disposal: does it induce autoantibodies in SLE? Ann Rheum Dis 2003; 62(1): 1-3.
[http://dx.doi.org/10.1136/ard.62.1.1-a] [PMID: 12480659]
[6]
Giles BM, Boackle SA. Linking complement and anti-dsDNA antibodies in the pathogenesis of systemic lupus erythematosus. Immunol Res 2013; 55(1-3): 10-21.
[http://dx.doi.org/10.1007/s12026-012-8345-z] [PMID: 22941560]
[7]
Yap DY, Lai KN. The role of cytokines in the pathogenesis of systemic lupus erythematosus - from bench to bedside. Nephrology (Carlton) 2013; 18(4): 243-55.
[http://dx.doi.org/10.1111/nep.12047] [PMID: 23452295]
[8]
Murugaiyan G, Mittal A, Weiner HL. Increased osteopontin expression in dendritic cells amplifies IL-17 production by CD4+ T cells in experimental autoimmune encephalomyelitis and in multiple sclerosis. J Immunol 2008; 181(11): 7480-8.
[http://dx.doi.org/10.4049/jimmunol.181.11.7480] [PMID: 19017937]
[9]
Kawaguchi M, Adachi M, Oda N, Kokubu F, Huang SK. IL-17 cytokine family. J Allergy Clin Immunol 2004; 114(6): 1265-73.
[http://dx.doi.org/10.1016/j.jaci.2004.10.019] [PMID: 15577820]
[10]
Nalbandian A, Crispín JC, Tsokos GC. Interleukin-17 and systemic lupus erythematosus: current concepts. Clin Exp Immunol 2009; 157(2): 209-15.
[http://dx.doi.org/10.1111/j.1365-2249.2009.03944.x] [PMID: 19604260]
[11]
Chen L, Morris DL, Vyse TJ. Genetic advances in systemic lupus erythematosus: an update. Curr Opin Rheumatol 2017; 29(5): 423-33.
[http://dx.doi.org/10.1097/BOR.0000000000000411] [PMID: 28509669]
[12]
Tao X, Lipsky PE. The Chinese anti-inflammatory and immunosuppressive herbal remedy Tripterygium wilfordii Hook F. Rheum Dis Clin North Am 2000; 26(1): 29-50 viii.
[http://dx.doi.org/10.1016/S0889-857X(05)70118-6] [PMID: 10680192]
[13]
Gu WZ, Banerjee S, Rauch J, Brandwein SR. Suppression of renal disease and arthritis, and prolongation of survival in MRL-lpr mice treated with an extract of Tripterygium wilfordii Hook f. Arthritis Rheum 1992; 35(11): 1381-6.
[http://dx.doi.org/10.1002/art.1780351122] [PMID: 1445458]
[14]
Tsokos GC. Systemic lupus erythematosus. N Engl J Med 2011; 365(22): 2110-21.
[http://dx.doi.org/10.1056/NEJMra1100359] [PMID: 22129255]
[15]
Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell 2008; 133(5): 775-87.
[http://dx.doi.org/10.1016/j.cell.2008.05.009] [PMID: 18510923]
[16]
Pan W, Zhu S, Dai D, et al. MiR-125a targets effector programs to stabilize Treg-mediated immune homeostasis. Nat Commun 2015; 6: 7096.
[http://dx.doi.org/10.1038/ncomms8096] [PMID: 25963922]
[17]
Qiu D, Zhao G, Aoki Y, et al. Immunosuppressant PG490 (triptolide) inhibits T-cell interleukin-2 expression at the level of purine-box/nuclear factor of activated T-cells and NF-kappaB transcriptional activation. J Biol Chem 1999; 274(19): 13443-50.
[http://dx.doi.org/10.1074/jbc.274.19.13443] [PMID: 10224109]
[18]
von Spee-Mayer C, Siegert E, Abdirama D, et al. Low-dose interleukin-2 selectively corrects regulatory T cell defects in patients with systemic lupus erythematosus. Ann Rheum Dis 2016; 75(7): 1407-15.
[http://dx.doi.org/10.1136/annrheumdis-2015-207776] [PMID: 26324847]
[19]
Endoh A, Kristiansen SB, Casson PR, Buster JE, Hornsby PJ. The zona reticularis is the site of biosynthesis of dehydroepiandrosterone and dehydroepiandrosterone sulfate in the adult human adrenal cortex resulting from its low expression of 3 beta-hydroxysteroid dehydrogenase. J Clin Endocrinol Metab 1996; 81(10): 3558-65.
[PMID: 8855801]
[20]
Takahashi H, Nakajima A, Sekihara H. Dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) inhibit the apoptosis in human peripheral blood lymphocytes. J Steroid Biochem Mol Biol 2004; 88(3): 261-4.
[http://dx.doi.org/10.1016/j.jsbmb.2003.12.006] [PMID: 15120419]
[21]
Liang J, Yao G, Yang L, Hou Y. Dehydroepiandrosterone induces apoptosis of thymocyte through Fas/Fas-L pathway. Int Immunopharmacol 2004; 4(12): 1467-75.
[http://dx.doi.org/10.1016/j.intimp.2004.06.010] [PMID: 15351316]
[22]
Petri M. Epidemiology of systemic lupus erythematosus. Best Pract Res Clin Rheumatol 2002; 16(5): 847-58.
[http://dx.doi.org/10.1053/berh.2002.0259] [PMID: 12473278]
[23]
Foo YZ, Nakagawa S, Rhodes G, Simmons LW. The effects of sex hormones on immune function: a meta-analysis. Biol Rev Camb Philos Soc 2017; 92(1): 551-71.
[http://dx.doi.org/10.1111/brv.12243] [PMID: 26800512]
[24]
Grover V, Jain A, Kapoor A, Malhotra R, Chahal GS. The gender bender effect in periodontal immune response. Endocr Metab Immune Disord Drug Targets 2016; 16(1): 12-20.
[http://dx.doi.org/10.2174/1871530316666160107111301] [PMID: 26739959]
[25]
Kissick HT, Sanda MG, Dunn LK, et al. Androgens alter T-cell immunity by inhibiting T-helper 1 differentiation. Proc Natl Acad Sci USA 2014; 111(27): 9887-92.
[http://dx.doi.org/10.1073/pnas.1402468111] [PMID: 24958858]
[26]
Golder V, Hoi A. Systemic lupus erythematosus: an update. Med J Aust 2017; 206(5): 215-20.
[http://dx.doi.org/10.5694/mja16.01229] [PMID: 28301792]
[27]
Addobbati C, de Azevêdo Silva J, Tavares NA, et al. Ficolin gene polymorphisms in systemic lupus erythematosus and rheumatoid arthritis. Ann Hum Genet 2016; 80(1): 1-6.
[http://dx.doi.org/10.1111/ahg.12129] [PMID: 26464189]
[28]
Kelly M, McCarthy S, Sahm LJ. Knowledge, attitudes and beliefs of patients and carers regarding medication adherence: a review of qualitative literature. Eur J Clin Pharmacol 2014; 70(12): 1423-31.
[http://dx.doi.org/10.1007/s00228-014-1761-3] [PMID: 25277162]
[29]
Beusterien K, Bell JA, Grinspan J, Utset TO, Kan H, Narayanan S. Physician-patient interactions and outcomes in systemic lupus erythematosus (SLE): a conceptual model. Lupus 2013; 22(10): 1038-45.
[http://dx.doi.org/10.1177/0961203313499958] [PMID: 23963432]
[30]
Truszewska A, Foroncewicz B, Pączek L. The role and diagnostic value of cell-free DNA in systemic lupus erythematosus. Clin Exp Rheumatol 2017; 35(2): 330-6.
[PMID: 27908304]
[31]
Mosca M, Tani C, Carli L, Bombardieri S. Glucocorticoids in systemic lupus erythematosus. Clin Exp Rheumatol 2011; 29(5)(Suppl. 68): S126-9.
[PMID: 22018198]
[32]
Luijten RK, Fritsch-Stork RD, Bijlsma JW, Derksen RH. The use of glucocorticoids in systemic lupus erythematosus. After 60 years still more an art than science. Autoimmun Rev 2013; 12(5): 617-28.
[http://dx.doi.org/10.1016/j.autrev.2012.12.001] [PMID: 23232124]
[33]
Apostolopoulos D, Kandane-Rathnayake R, Raghunath S, Hoi A, Nikpour M, Morand EF. Independent association of glucocorticoids with damage accrual in SLE. Lupus Sci Med 2016; 3(1)e000157
[http://dx.doi.org/10.1136/lupus-2016-000157] [PMID: 27933196]
[34]
Borchers AT, Keen CL, Shoenfeld Y, Gershwin ME. Surviving the butterfly and the wolf: mortality trends in systemic lupus erythematosus. Autoimmun Rev 2004; 3(6): 423-53.
[http://dx.doi.org/10.1016/j.autrev.2004.04.002] [PMID: 15351310]
[35]
Askanase AD, Yazdany J, Molta CT. Post-marketing experiences with belimumab in the treatment of SLE patients Rheum Dis Clin North Am 2014; 40(3): 507-17 viii.
[http://dx.doi.org/10.1016/j.rdc.2014.04.007] [PMID: 25034159]
[36]
Hahn BH. Belimumab for systemic lupus erythematosus. N Engl J Med 2013; 368(16): 1528-35.
[http://dx.doi.org/10.1056/NEJMct1207259] [PMID: 23594005]
[37]
Horowitz DL, Furie R. Belimumab is approved by the FDA: what more do we need to know to optimize decision making? Curr Rheumatol Rep 2012; 14(4): 318-23.
[http://dx.doi.org/10.1007/s11926-012-0256-4] [PMID: 22535566]
[38]
Navarra SV, Guzmán RM, Gallacher AE, et al. BLISS-52 Study Group Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet 2011; 377(9767): 721-31.
[http://dx.doi.org/10.1016/S0140-6736(10)61354-2] [PMID: 21296403]
[39]
Furtado J, Isenberg DA. B cell elimination in systemic lupus erythematosus. Clin Immunol 2013; 146(2): 90-103.
[http://dx.doi.org/10.1016/j.clim.2012.11.006] [PMID: 23280492]
[40]
Straub RH, Lehle K, Herfarth H, et al. Dehydroepiandrosterone in relation to other adrenal hormones during an acute inflammatory stressful disease state compared with chronic inflammatory disease: role of interleukin-6 and tumour necrosis factor. Eur J Endocrinol 2002; 146(3): 365-74.
[http://dx.doi.org/10.1530/eje.0.1460365] [PMID: 11888843]
[41]
Dillon JS. Dehydroepiandrosterone, dehydroepiandrosterone sulfate and related steroids: their role in inflammatory, allergic and immunological disorders. Curr Drug Targets Inflamm Allergy 2005; 4(3): 377-85.
[http://dx.doi.org/10.2174/1568010054022079] [PMID: 16101547]
[42]
Durcan L, Petri M. Immunomodulators in SLE: Clinical evidence and immunologic actions. J Autoimmun 2016; 74: 73-84.
[http://dx.doi.org/10.1016/j.jaut.2016.06.010] [PMID: 27371107]
[43]
Huang X, Wen C, Wei H. Therapeutic effects of triptolide on Lupus-prone MRL/lpr Mice. Int J Pharmacol 2018; 14: 681-8.
[http://dx.doi.org/10.3923/ijp.2018.681.688]
[44]
He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 2004; 5(7): 522-31.
[http://dx.doi.org/10.1038/nrg1379] [PMID: 15211354]
[45]
Liston A, Lu LF, O’Carroll D, Tarakhovsky A, Rudensky AY. Dicer-dependent microRNA pathway safeguards regulatory T cell function. J Exp Med 2008; 205(9): 1993-2004.
[http://dx.doi.org/10.1084/jem.20081062] [PMID: 18725526]
[46]
Liu L, Liu Y, Yuan M, Xu L, Sun H. Elevated expression of microRNA-873 facilitates Th17 differentiation by targeting forkhead box O1 (Foxo1) in the pathogenesis of systemic lupus erythematosus. Biochem Biophys Res Commun 2017; 492(3): 453-60.
[http://dx.doi.org/10.1016/j.bbrc.2017.08.075] [PMID: 28837808]
[47]
Zheng Y, Josefowicz SZ, Kas A, Chu TT, Gavin MA, Rudensky AY. Genome-wide analysis of Foxp3 target genes in developing and mature regulatory T cells. Nature 2007; 445(7130): 936-40.
[http://dx.doi.org/10.1038/nature05563] [PMID: 17237761]
[48]
Littman DR, Rudensky AY. Th17 and regulatory T cells in mediating and restraining inflammation. Cell 2010; 140(6): 845-58.
[http://dx.doi.org/10.1016/j.cell.2010.02.021] [PMID: 20303875]
[49]
Liu Y, Yu Y, Matarese G, La Cava A. Cutting edge: fasting-induced hypoleptinemia expands functional regulatory T cells in systemic lupus erythematosus. J Immunol 2012; 188(5): 2070-3.
[http://dx.doi.org/10.4049/jimmunol.1102835] [PMID: 22291185]
[50]
Humrich JY, Morbach H, Undeutsch R, et al. Homeostatic imbalance of regulatory and effector T cells due to IL-2 deprivation amplifies murine lupus. Proc Natl Acad Sci USA 2010; 107(1): 204-9.
[http://dx.doi.org/10.1073/pnas.0903158107] [PMID: 20018660]
[51]
Li G, Ren J, Wang G, et al. T2 enhances in situ level of Foxp3+ regulatory cells and modulates inflammatory cytokines in Crohn’s disease. Int Immunopharmacol 2014; 18(2): 244-8.
[http://dx.doi.org/10.1016/j.intimp.2013.12.014] [PMID: 24369313]
[52]
Qiu D, Kao PN. Immunosuppressive and anti-inflammatory mechanisms of triptolide, the principal active diterpenoid from the Chinese medicinal herb Tripterygium wilfordii Hook. f. Drugs R D 2003; 4(1): 1-18.
[http://dx.doi.org/10.2165/00126839-200304010-00001] [PMID: 12568630]
[53]
Linker-Israeli M, Bakke AC, Kitridou RC, Gendler S, Gillis S, Horwitz DA. Defective production of interleukin 1 and interleukin 2 in patients with systemic lupus erythematosus (SLE). J Immunol 1983; 130(6): 2651-5.
[PMID: 6222112]
[54]
Li Y, Yu C, Zhu WM, et al. Triptolide ameliorates IL-10-deficient mice colitis by mechanisms involving suppression of IL-6/STAT3 signaling pathway and down-regulation of IL-17. Mol Immunol 2010; 47(15): 2467-74.
[http://dx.doi.org/10.1016/j.molimm.2010.06.007] [PMID: 20615550]
[55]
Qu B, Shen N. miRNAs in the pathogenesis of systemic lupus erythematosus. Int J Mol Sci 2015; 16(5): 9557-72.
[http://dx.doi.org/10.3390/ijms16059557] [PMID: 25927578]
[56]
Te JL, Dozmorov IM, Guthridge JM, et al. Identification of unique microRNA signature associated with lupus nephritis. PLoS One 2010; 5(5)e10344
[http://dx.doi.org/10.1371/journal.pone.0010344] [PMID: 20485490]
[57]
Jeoung D, Lim Y, Lee EB, et al. Identification of autoantibody against poly (ADP-ribose) polymerase (PARP) fragment as a serological marker in systemic lupus erythematosus. J Autoimmun 2004; 22(1): 87-94.
[http://dx.doi.org/10.1016/j.jaut.2003.10.009] [PMID: 14709417]
[58]
Boulares AH, Zoltoski AJ, Contreras FJ, Yakovlev AG, Yoshihara K, Smulson ME. Regulation of DNAS1L3 endonuclease activity by poly(ADP-ribosyl)ation during etoposide-induced apoptosis. Role of poly(ADP-ribose) polymerase-1 cleavage in endonuclease activation. J Biol Chem 2002; 277(1): 372-8.
[http://dx.doi.org/10.1074/jbc.M107738200] [PMID: 11694507]
[59]
Souliotis VL, Vougas K, Gorgoulis VG, Sfikakis PP. Defective DNA repair and chromatin organization in patients with quiescent systemic lupus erythematosus. Arthritis Res Ther 2016; 18(1): 182.
[http://dx.doi.org/10.1186/s13075-016-1081-3] [PMID: 27492607]
[60]
Rapoport MJ, Bloch O, Amit-Vasina M, Yona E, Molad Y. Constitutive abnormal expression of RasGRP-1 isoforms and low expression of PARP-1 in patients with systemic lupus erythematosus. Lupus 2011; 20(14): 1501-9.
[http://dx.doi.org/10.1177/0961203311418790] [PMID: 21976405]
[61]
Ethier C, Labelle Y, Poirier GG. PARP-1-induced cell death through inhibition of the MEK/ERK pathway in MNNG-treated HeLa cells. Apoptosis 2007; 12(11): 2037-49.
[http://dx.doi.org/10.1007/s10495-007-0127-z] [PMID: 17828454]
[62]
Bloch O, Amit-Vazina M, Yona E, Molad Y, Rapoport MJ. Increased ERK and JNK activation and decreased ERK/JNK ratio are associated with long-term organ damage in patients with systemic lupus erythematosus. Rheumatology (Oxford) 2014; 53(6): 1034-42.
[http://dx.doi.org/10.1093/rheumatology/ket482] [PMID: 24501249]
[63]
Arora V, Verma J, Marwah V, Kumar A, Anand D, Das N. Cytokine imbalance in systemic lupus erythematosus: a study on northern Indian subjects. Lupus 2012; 21(6): 596-603.
[http://dx.doi.org/10.1177/0961203311434937] [PMID: 22300832]
[64]
Qian C, Jiang X, An H, et al. TLR agonists promote ERK-mediated preferential IL-10 production of regulatory dendritic cells (diffDCs), leading to NK-cell activation. Blood 2006; 108(7): 2307-15.
[http://dx.doi.org/10.1182/blood-2006-03-005595] [PMID: 16778140]
[65]
Llorente L, Zou W, Levy Y, et al. Role of interleukin 10 in the B lymphocyte hyperactivity and autoantibody production of human systemic lupus erythematosus. J Exp Med 1995; 181(3): 839-44.
[http://dx.doi.org/10.1084/jem.181.3.839] [PMID: 7869046]
[66]
Alarcón-Segovia D, Tumlin JA, Furie RA, et al. LJP 394 Investigator Consortium. LJP 394 for the prevention of renal flare in patients with systemic lupus erythematosus: results from a randomized, double-blind, placebo-controlled study. Arthritis Rheum 2003; 48(2): 442-54.
[http://dx.doi.org/10.1002/art.10763] [PMID: 12571854]
[67]
Furie R. Safety, pharmacokinetic and pharmacodynamic results of a phase 1 single and double dose-escalation study of LymphoStat-B (human monoclonal antibody to BLyS) in SLE patient. Arthritis Rheum 2003; 48: S377.
[68]
Chang DM. Interleukin-1 and interleukin-1 receptor antagonist in systemic lupus erythematosus. Immunol Invest 1997; 26(5-7): 649-59.
[http://dx.doi.org/10.3109/08820139709088547] [PMID: 9399106]
[69]
Moosig F, Zeuner R, Renk C, Schröder JO. IL-1RA in refractory systemic lupus erythematosus. Lupus 2004; 13(8): 605-6.
[http://dx.doi.org/10.1191/0961203304lu1047cr] [PMID: 15462491]
[70]
Ostendorf B, Iking-Konert C, Kurz K, Jung G, Sander O, Schneider M. Preliminary results of safety and efficacy of the interleukin 1 receptor antagonist anakinra in patients with severe lupus arthritis. Ann Rheum Dis 2005; 64(4): 630-3.
[http://dx.doi.org/10.1136/ard.2004.025858] [PMID: 15345502]
[71]
Andersen LS, Petersen J, Svenson M, Bendtzen K. Production of IL-1β, IL-1 receptor antagonist and IL-10 by mononuclear cells from patients with SLE. Autoimmunity 1999; 30(4): 235-42.
[http://dx.doi.org/10.3109/08916939908993804] [PMID: 10524499]
[72]
Scuderi F, Convertino R, Molino N, et al. Effect of pro-inflammatory/anti-inflammatory agents on cytokine secretion by peripheral blood mononuclear cells in rheumatoid arthritis and systemic lupus erythematosus. Autoimmunity 2003; 36(2): 71-7.
[http://dx.doi.org/10.1080/0891693031000079275] [PMID: 12820688]
[73]
Sturfelt G, Roux-Lombard P, Wollheim FA, Dayer JM. Low levels of interleukin-1 receptor antagonist coincide with kidney involvement in systemic lupus erythematosus. Br J Rheumatol 1997; 36(12): 1283-9.
[http://dx.doi.org/10.1093/rheumatology/36.12.1283] [PMID: 9448589]

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