Abstract
Peptic ulcer disease (PUD) is a widespread condition that affects millions of people each year, with an incidence rate of 0.1%-1.5%, and has a significant impact on human health. A range of stimuli, such as Helicobacter pylori, non-steroidal anti-inflammatory drugs, hyperacidity, stress, alcohol, smoking, and idiopathic disease states, can produce a sore in the gastrointestinal mucosal layer. For individuals infected with H. pylori, 2%-3% remain asymptomatic throughout their life. Although PUD treatments are available, genetic variations occurring in individuals because of geographical dissimilarity and antibiotic resistance pose limitations. Specifically, inflammatory cytokine gene polymorphisms have received immense attention in recent years because they appear to affect the severity and duration of stomach inflammation, which is induced by H. pylori infection, contributing to the initiation of PUD. In such a context, in-depth knowledge of interleukins may aid in the discovery of new targets and provide precautionary approaches for the treatment of PUD. This review aims to give insights into the importance of several interleukins that cognate with PUD and contribute to ulcer progression or healing by activating or dampening the host immunity. Furthermore, the available targets with clinical evidence have been explored in this review.
Keywords: Peptic ulcer disease, inflammation, cytokines, Helicobacter pylori, gastritis, host immunity.
Graphical Abstract
[http://dx.doi.org/10.1177/1203475419858955] [PMID: 31253050]
[http://dx.doi.org/10.1016/j.jtv.2013.08.001] [PMID: 23993047]
[http://dx.doi.org/10.1080/00325481.2020.1795485] [PMID: 32654578]
[http://dx.doi.org/10.1016/j.amjmed.2018.12.009] [PMID: 30611829]
[http://dx.doi.org/10.1136/gutjnl-2019-318715] [PMID: 31229990]
[http://dx.doi.org/10.1111/j.1572-0241.2002.07068.x] [PMID: 12492176]
[http://dx.doi.org/10.1111/j.1365-2249.2008.03859.x] [PMID: 19210519]
[http://dx.doi.org/10.3389/fimmu.2022.826106] [PMID: 35281071]
[http://dx.doi.org/10.1080/19490976.2015.1105427] [PMID: 26727421]
[http://dx.doi.org/10.1136/gutjnl-2014-307175] [PMID: 26079943]
[http://dx.doi.org/10.1177/1753425917738043] [PMID: 29145789]
[http://dx.doi.org/10.1016/j.cell.2014.04.007] [PMID: 24855941]
[http://dx.doi.org/10.1172/JCI79337] [PMID: 26214524]
[http://dx.doi.org/10.1038/sigtrans.2017.23] [PMID: 29158945]
[http://dx.doi.org/10.4049/jimmunol.1502261] [PMID: 27084101]
[http://dx.doi.org/10.3164/jcbn.10-79] [PMID: 21373261]
[http://dx.doi.org/10.5152/eurasianjmed.2018.0010] [PMID: 30002579]
[http://dx.doi.org/10.3389/fimmu.2018.00074] [PMID: 29441064]
[http://dx.doi.org/10.1016/j.oraloncology.2016.10.001] [PMID: 27720397]
[http://dx.doi.org/10.1016/j.drugalcdep.2017.11.013] [PMID: 29289868]
[http://dx.doi.org/10.1177/0148607190014006615] [PMID: 2125645140]
[http://dx.doi.org/10.1186/s12876-016-0554-9] [PMID: 27894275]
[http://dx.doi.org/10.18632/oncotarget.11449] [PMID: 27602578]
[http://dx.doi.org/10.1111/hel.12501] [PMID: 29938865]
[http://dx.doi.org/10.2174/1389450121666201027124625] [PMID: 33109042]
[http://dx.doi.org/10.1016/j.compositesb.2021.109393]
[http://dx.doi.org/10.3389/fimmu.2015.00466] [PMID: 26441971]
[http://dx.doi.org/10.1016/j.cellsig.2018.10.005] [PMID: 30312659]
[http://dx.doi.org/10.1016/j.jid.2018.07.025] [PMID: 30120937]
[http://dx.doi.org/10.1007/s11892-014-0553-6] [PMID: 25344788]
[PMID: 27987522]
[http://dx.doi.org/10.2147/ITT.S214139] [PMID: 32548074]
[http://dx.doi.org/10.1111/1440-1681.12946] [PMID: 29655253]
[http://dx.doi.org/10.1111/bjd.17869] [PMID: 30851191]
[http://dx.doi.org/10.1007/s13277-016-5098-7] [PMID: 27260630]
[http://dx.doi.org/10.3389/fgene.2022.822091] [PMID: 35368692]
[http://dx.doi.org/10.1016/j.neuint.2018.10.012] [PMID: 30342072]
[http://dx.doi.org/10.1016/j.archoralbio.2018.09.015] [PMID: 30290294]
[http://dx.doi.org/10.1159/000512965] [PMID: 33486487]
[http://dx.doi.org/10.1186/s13223-019-0332-7] [PMID: 30911316]
[http://dx.doi.org/10.1016/j.ejim.2019.04.012] [PMID: 31036439]
[http://dx.doi.org/10.1016/j.clinthera.2017.01.030] [PMID: 28237672]
[http://dx.doi.org/10.1002/iub.1637] [PMID: 28474494]
[http://dx.doi.org/10.1620/tjem.247.87] [PMID: 30773517]
[http://dx.doi.org/10.1038/s41584-018-0044-2] [PMID: 30006601]
[http://dx.doi.org/10.1016/j.jneuroim.2019.577071] [PMID: 31671361]
[http://dx.doi.org/10.1007/s00403-016-1638-7] [PMID: 26969580]
[http://dx.doi.org/10.3390/ijms18040783] [PMID: 28387719]
[http://dx.doi.org/10.3390/ijms20236008] [PMID: 31795299]
[http://dx.doi.org/10.3233/JAD-200711] [PMID: 33016914]
[http://dx.doi.org/10.1517/14712598.2015.1044434] [PMID: 25947043]
[http://dx.doi.org/10.1080/14728222.2017.1258402] [PMID: 27817222]
[http://dx.doi.org/10.1016/j.disamonth.2018.09.011] [PMID: 30384973]
[http://dx.doi.org/10.1186/s40249-020-00666-7] [PMID: 32381058]
[http://dx.doi.org/10.1038/s41598-020-71371-6] [PMID: 32884012]
[http://dx.doi.org/10.1186/s41232-019-0101-5]
[http://dx.doi.org/10.1016/j.bjid.2018.06.005] [PMID: 30048609]
[http://dx.doi.org/10.1038/nrgastro.2014.99] [PMID: 25001975]
[http://dx.doi.org/10.1111/j.1751-2980.2009.00380.x] [PMID: 19659782]
[http://dx.doi.org/10.1371/journal.pone.0176463] [PMID: 28453551]
[http://dx.doi.org/10.1084/jem.28.2.223] [PMID: 19868252]
[http://dx.doi.org/10.1210/js.2019-00053] [PMID: 31259292]
[http://dx.doi.org/10.3748/wjg.v16.i10.1188] [PMID: 20222161]
[http://dx.doi.org/10.1016/S1734-1140(13)70971-X] [PMID: 23563031]
[http://dx.doi.org/10.4236/fns.2011.26088]
[http://dx.doi.org/10.1016/j.jmii.2015.03.002] [PMID: 25888319]
[http://dx.doi.org/10.1177/147323000303100202] [PMID: 12760309]
[http://dx.doi.org/10.1038/nm1282] [PMID: 16041381]
[http://dx.doi.org/10.18821/1560-9529-2019-24-1-4-10]
[http://dx.doi.org/10.1111/j.1600-065X.2008.00706.x] [PMID: 19161426]
[http://dx.doi.org/10.1146/annurev-immunol-031210-101312] [PMID: 21166540]
[http://dx.doi.org/10.1111/prd.12083] [PMID: 26252407]
[http://dx.doi.org/10.1038/mi.2009.138] [PMID: 20032970]
[http://dx.doi.org/10.1177/154405910808700908] [PMID: 18719207]
[http://dx.doi.org/10.1186/1479-5876-9-111] [PMID: 21762495]
[http://dx.doi.org/10.4049/jimmunol.1200385] [PMID: 22566565]
[http://dx.doi.org/10.1146/annurev.immunol.021908.132612] [PMID: 19302047]
[http://dx.doi.org/10.1074/jbc.M114.577429] [PMID: 25183005]
[PMID: 30535468]
[http://dx.doi.org/10.1038/ni.2055] [PMID: 21772279]
[http://dx.doi.org/10.3390/toxins13050315] [PMID: 33924897]
[http://dx.doi.org/10.1007/s10787-017-0380-x] [PMID: 28735449]
[http://dx.doi.org/10.3390/cells8101290] [PMID: 31640262]
[http://dx.doi.org/10.4292/wjgpt.v7.i1.126] [PMID: 26855818]
[http://dx.doi.org/10.3389/fphar.2022.817237] [PMID: 35237167]
[http://dx.doi.org/10.1515/bmc-2020-0006]
[http://dx.doi.org/10.5455/njppp.2018.8.0309317072017]
[http://dx.doi.org/10.1016/j.lfs.2019.116607] [PMID: 31254582]
[http://dx.doi.org/10.1016/j.phrs.2020.104846] [PMID: 32339784]
[http://dx.doi.org/10.3389/fphys.2020.00694] [PMID: 32714204]
[http://dx.doi.org/10.1016/j.jcmgh.2017.02.002]
[http://dx.doi.org/10.1016/j.bbagen.2013.03.013] [PMID: 23523691]
[http://dx.doi.org/10.1002/ptr.5210] [PMID: 25069887]
[http://dx.doi.org/10.1089/ars.2011.4232] [PMID: 21942294]
[http://dx.doi.org/10.1016/j.biopha.2020.110075] [PMID: 32179202]
[http://dx.doi.org/10.1155/2013/136932] [PMID: 24066235]
[http://dx.doi.org/10.1007/s00210-020-01894-2]
[http://dx.doi.org/10.1007/s10620-011-1761-4] [PMID: 21633832]
[http://dx.doi.org/10.1111/j.1523-5378.2008.00593.x] [PMID: 18321302]
[http://dx.doi.org/10.3748/wjg.v18.i45.6521] [PMID: 23236223]