Abstract
Interleukin-10 (IL-10) is an important immunomodulatory cytokine, initially characterized as an anti-inflammatory agent released by immune cells during infectious and inflammatory processes. IL-10 exhibits biological functions that extend to the regulation of different intracellular signaling pathways directly associated with vascular function. This cytokine plays a vital role in vascular tone regulation by changing important proteins involved in vasoconstriction and vasodilation. Numerous investigations covered here have shown that therapeutic strategies inducing IL-10 exert anti-inflammatory, anti-hypertrophic, anti-hyperplastic, anti-apoptotic and antihypertensive effects. This non-systematic review summarizes the modulating effects mediated by IL-10 in vascular tissue, particularly on vascular tone, and the intracellular pathway induced by this cytokine. We also highlight the advances in IL-10 manipulation as a therapeutic target in different cardiovascular pathophysiologies, including the physiological implications in animals and humans. Finally, the review illustrates current and potential future perspectives of the potential use of IL-10 in clinical trials based on the clinical evidence.
Keywords: Interleukin-10, cytokine, anti-inflammatory, contraction, vasodilation, cardiovascular diseases.
[http://dx.doi.org/10.1084/jem.170.6.2081] [PMID: 2531194]
[http://dx.doi.org/10.1016/j.immuni.2019.03.020] [PMID: 30995504]
[http://dx.doi.org/10.1016/j.cytogfr.2010.11.001] [PMID: 21112807]
[http://dx.doi.org/10.3389/fncel.2018.00458] [PMID: 30542269]
[http://dx.doi.org/10.1016/j.jaci.2008.02.026] [PMID: 18405958]
[http://dx.doi.org/10.1146/annurev-immunol-031210-101312] [PMID: 21166540]
[http://dx.doi.org/10.1155/2015/764641] [PMID: 26199463]
[PMID: 7543512]
[http://dx.doi.org/10.3892/mmr.2018.9547] [PMID: 30320384]
[http://dx.doi.org/10.1074/jbc.274.23.16513] [PMID: 10347215]
[http://dx.doi.org/10.3389/fcvm.2019.00150] [PMID: 31709266]
[http://dx.doi.org/10.1016/j.cytogfr.2016.05.001] [PMID: 27185365]
[http://dx.doi.org/10.1093/bfgp/elt028] [PMID: 23943603]
[http://dx.doi.org/10.1101/cshperspect.a011205] [PMID: 22383755]
[http://dx.doi.org/10.4049/jimmunol.178.5.2623] [PMID: 17312100]
[http://dx.doi.org/10.1007/s42000-018-0078-5] [PMID: 30414080]
[http://dx.doi.org/10.3389/fimmu.2014.00058] [PMID: 24600449]
[http://dx.doi.org/10.4081/ejh.2019.3054] [PMID: 31833328]
[http://dx.doi.org/10.3389/fimmu.2019.01267] [PMID: 31214200]
[http://dx.doi.org/10.1016/j.coph.2006.01.010] [PMID: 16713356]
[http://dx.doi.org/10.1016/j.smim.2013.12.004] [PMID: 24418198]
[http://dx.doi.org/10.4172/2155-6156.S13-003]
[http://dx.doi.org/10.1096/fasebj.27.1_supplement.1128.5]
[http://dx.doi.org/10.1038/cddis.2016.44] [PMID: 26962683]
[http://dx.doi.org/10.1016/j.lfs.2020.118552] [PMID: 33035583]
[http://dx.doi.org/10.1016/j.lfs.2018.07.058] [PMID: 30075176]
[http://dx.doi.org/10.1046/j.1365-2141.2000.01925.x] [PMID: 10759705]
[http://dx.doi.org/10.1006/cyto.1995.0008] [PMID: 8742067]
[http://dx.doi.org/10.1161/ATVBAHA.111.233262] [PMID: 21817097]
[http://dx.doi.org/10.1038/nri2711] [PMID: 20154735]
[http://dx.doi.org/10.1016/j.vph.2021.106838] [PMID: 33540122]
[http://dx.doi.org/10.1111/j.1600-065X.2008.00706.x] [PMID: 19161426]
[http://dx.doi.org/10.1016/j.jss.2004.03.025] [PMID: 15501460]
[http://dx.doi.org/10.1016/j.immuni.2011.03.016] [PMID: 21530328]
[http://dx.doi.org/10.1016/j.molimm.2013.10.006] [PMID: 24246800]
[http://dx.doi.org/10.3389/fimmu.2020.00083] [PMID: 32210950]
[http://dx.doi.org/10.1016/j.abb.2017.01.001] [PMID: 28063948]
[http://dx.doi.org/10.1126/science.aal3535]
[http://dx.doi.org/10.1073/pnas.0502407102] [PMID: 15878989]
[http://dx.doi.org/10.1161/CIRCRESAHA.108.188243] [PMID: 19096025]
[http://dx.doi.org/10.1152/ajpheart.00918.2003]
[http://dx.doi.org/10.3346/jkms.2008.23.1.89] [PMID: 18303205]
[http://dx.doi.org/10.1016/j.lfs.2015.12.009] [PMID: 26682936]
[http://dx.doi.org/10.1038/gt.2008.151] [PMID: 18818668]
[http://dx.doi.org/10.4049/jimmunol.1100060] [PMID: 21602495]
[PMID: 25337228]
[http://dx.doi.org/10.1111/j.1468-1331.2004.00986.x] [PMID: 15693810]
[http://dx.doi.org/10.1111/bjd.15158] [PMID: 28581220]
[http://dx.doi.org/10.1016/S0165-2427(02)00068-5]
[http://dx.doi.org/10.1111/bph.14436] [PMID: 29969833]
[http://dx.doi.org/10.1002/cphy.c200020] [PMID: 33577121]
[http://dx.doi.org/10.1016/j.phrs.2017.01.010] [PMID: 28093357]
[http://dx.doi.org/10.1152/ajpheart.1982.243.5.H641]
[http://dx.doi.org/10.1101/cshperspect.a023200] [PMID: 29419405]
[http://dx.doi.org/10.1093/cvr/cvy023] [PMID: 29394331]
[http://dx.doi.org/10.1152/advances.2003.27.4.201] [PMID: 14627618]
[http://dx.doi.org/10.1124/pr.115.010652] [PMID: 27037223]
[http://dx.doi.org/10.1152/ajpheart.00251.2008] [PMID: 19074677]
[http://dx.doi.org/10.1097/MIB.0000000000000468] [PMID: 26164667]
[http://dx.doi.org/10.1152/ajpheart.2000.279.4.H1555] [PMID: 11009441]
[http://dx.doi.org/10.3389/fphar.2015.00149] [PMID: 26257652]
[http://dx.doi.org/10.1161/hh2001.098873] [PMID: 11597988]
[http://dx.doi.org/10.1016/S0014-5793(99)00641-9] [PMID: 10386601]
[http://dx.doi.org/10.22088/IJMCM.BUMS.9.1.50] [PMID: 32832484]
[http://dx.doi.org/10.1182/blood-2002-05-1525] [PMID: 12393419]
[http://dx.doi.org/10.1002/eji.200526192] [PMID: 16184516]
[http://dx.doi.org/10.1111/fcp.12409]
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.109.140459] [PMID: 19901158]
[http://dx.doi.org/10.1111/fcp.12409]
[http://dx.doi.org/10.1016/j.lfs.2016.01.022] [PMID: 26775566]
[http://dx.doi.org/10.1016/j.pathophys.2005.02.007] [PMID: 15927823]
[http://dx.doi.org/10.1016/bs.apha.2016.09.001]
[http://dx.doi.org/10.1007/s11906-018-0835-5] [PMID: 29736674]
[http://dx.doi.org/10.1161/01.HYP.8.1.37] [PMID: 3080370]
[http://dx.doi.org/10.1152/japplphysiol.00446.2013] [PMID: 23788575]
[http://dx.doi.org/10.1016/S0008-6363(99)00115-7] [PMID: 10690324]
[http://dx.doi.org/10.1152/ajpheart.00129.2003]
[http://dx.doi.org/10.1007/5584_2016_90] [PMID: 28035582]
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.109.137158] [PMID: 19620507]
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.117.09401] [PMID: 28847894]
[http://dx.doi.org/10.1139/Y08-049] [PMID: 18758504]
[http://dx.doi.org/10.1016/j.jacc.2004.02.054] [PMID: 15234404]
[http://dx.doi.org/10.1152/ajpheart.01234.2004]
[http://dx.doi.org/10.4049/jimmunol.177.7.4888] [PMID: 16982931]
[http://dx.doi.org/10.3109/07853899509002465] [PMID: 8541028]
[http://dx.doi.org/10.1161/ATVBAHA.117.310672] [PMID: 29880489]
[http://dx.doi.org/10.1016/S0022-4804(03)00144-6] [PMID: 12888334]
[http://dx.doi.org/10.1002/jgm.1166] [PMID: 18205252]
[http://dx.doi.org/10.1161/CIRCRESAHA.107.153023] [PMID: 17673672]
[http://dx.doi.org/10.1681/ASN.2005030297] [PMID: 16251240]
[http://dx.doi.org/10.1152/ajprenal.00206.2020] [PMID: 32686523]
[http://dx.doi.org/10.1016/j.cyto.2018.07.003] [PMID: 30539780]
[http://dx.doi.org/10.1152/ajpregu.00712.2009] [PMID: 20053959]
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.14406] [PMID: 32078397]
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.114.03663] [PMID: 24935938]
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.116.06602] [PMID: 27777357]
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.14089] [PMID: 32336228]
[http://dx.doi.org/10.1007/s11906-019-0959-2] [PMID: 31123838]
[http://dx.doi.org/10.1038/hr.2015.62] [PMID: 25971630]
[http://dx.doi.org/10.1016/j.cyto.2014.02.008] [PMID: 24656930]
[http://dx.doi.org/10.1161/01.CIR.101.9.1019] [PMID: 10704170]
[http://dx.doi.org/10.1371/journal.pone.0147615] [PMID: 26808574]
[http://dx.doi.org/10.1161/CIRCRESAHA.111.248369] [PMID: 21959218]
[http://dx.doi.org/10.1007/s00417-016-3427-6] [PMID: 27405975]
[http://dx.doi.org/10.1096/fj.12-215442] [PMID: 23070607]
[http://dx.doi.org/10.1096/fj.09-148155] [PMID: 20354139]
[http://dx.doi.org/10.2337/diabetes.53.4.1060] [PMID: 15047622]
[http://dx.doi.org/10.2337/db08-1261] [PMID: 19690064]
[http://dx.doi.org/10.1038/mt.2013.125] [PMID: 23774795]
[http://dx.doi.org/10.1038/s41574-019-0176-8] [PMID: 30814686]
[http://dx.doi.org/10.1016/j.cyto.2004.10.017] [PMID: 15749027]
[http://dx.doi.org/10.1111/bph.13666] [PMID: 27976387]
[http://dx.doi.org/10.1210/jc.2019-00341] [PMID: 31132124]
[http://dx.doi.org/10.1007/s00232-017-9974-x] [PMID: 28776087]
[http://dx.doi.org/10.4049/jimmunol.167.7.4075] [PMID: 11564829]
[http://dx.doi.org/10.1126/sciadv.aaz0748] [PMID: 32851154]
[http://dx.doi.org/10.1016/j.biomaterials.2019.02.017] [PMID: 30852423]
[http://dx.doi.org/10.1093/infdis/jiz254] [PMID: 31077265]
[http://dx.doi.org/10.1161/01.CIR.0000065232.57371.25] [PMID: 12668510]
[http://dx.doi.org/10.1016/j.coi.2014.12.009] [PMID: 25597442]
[http://dx.doi.org/10.1007/BF03402102] [PMID: 12765335]
[PMID: 7730651]
[http://dx.doi.org/10.1186/ar2814] [PMID: 19781067]
[http://dx.doi.org/10.1002/1529-0131(200008)43:8<1790::AID-ANR15>3.0.CO;2-2] [PMID: 10943869]
[PMID: 24750799]
[http://dx.doi.org/10.1046/j.1365-2036.2001.01093.x] [PMID: 11683684]
[http://dx.doi.org/10.1053/gast.2000.20822] [PMID: 11113101]
[http://dx.doi.org/10.1007/s11912-019-0760-z] [PMID: 30790069]
[http://dx.doi.org/10.1055/s-0031-1297959] [PMID: 22187388]
[http://dx.doi.org/10.1097/HCR.0000000000000377] [PMID: 30586113]
[PMID: 18751625]
[http://dx.doi.org/10.1097/MAJ.0000000000000378] [PMID: 25635749]
[http://dx.doi.org/10.1177/2050312120965752] [PMID: 33194199]
[http://dx.doi.org/10.1159/000204114] [PMID: 7639054]
[http://dx.doi.org/10.1007/s00296-003-0289-0] [PMID: 12634936]
[http://dx.doi.org/10.2143/AC.60.6.2004938] [PMID: 16385927]
[http://dx.doi.org/10.37358/RC.19.10.7581]
[http://dx.doi.org/10.1056/NEJMra035363] [PMID: 15028825]
[http://dx.doi.org/10.1182/blood.V98.9.2720] [PMID: 11675343]
[http://dx.doi.org/10.1007/BF01419947] [PMID: 8783415]
[http://dx.doi.org/10.1016/j.cca.2019.05.006] [PMID: 31075237]
[http://dx.doi.org/10.1210/jc.2002-021437] [PMID: 12629085]
[http://dx.doi.org/10.1210/jc.2005-0281] [PMID: 16030165]
[http://dx.doi.org/10.1155/2015/493409] [PMID: 25944984]
[PMID: 19848048]
[http://dx.doi.org/10.1016/j.tem.2014.02.004] [PMID: 24698032]
[http://dx.doi.org/10.1152/ajpheart.01327.2005]
[http://dx.doi.org/10.1046/j.1365-2362.2002.01069.x] [PMID: 12423320]
[http://dx.doi.org/10.5372/10463]
[http://dx.doi.org/10.1253/circj.CJ-09-0801] [PMID: 20339193]
[http://dx.doi.org/10.1038/s41598-018-25856-0] [PMID: 29765083]
[http://dx.doi.org/10.1016/j.jvs.2016.01.055] [PMID: 26994954]
[http://dx.doi.org/10.1016/j.ejcts.2008.12.037] [PMID: 19211261]
[http://dx.doi.org/10.1093/ejcts/ezs145] [PMID: 22466697]
[http://dx.doi.org/10.2215/CJN.08660813] [PMID: 24789549]
[http://dx.doi.org/10.1046/j.1523-1755.2002.00504.x] [PMID: 12164877]
[http://dx.doi.org/10.1371/journal.pone.0230551] [PMID: 32255785]
[http://dx.doi.org/10.1007/s10103-016-2115-4] [PMID: 27924419]
[http://dx.doi.org/10.1016/j.jaci.2010.03.008.Decreased]
[http://dx.doi.org/10.1165/rcmb.2007-0014OC] [PMID: 18314542]
[http://dx.doi.org/10.1016/S0003-4975(03)00194-2] [PMID: 12842524]
[http://dx.doi.org/10.1681/ASN.2014080764] [PMID: 25855775]
[http://dx.doi.org/10.1016/j.wneu.2019.05.102] [PMID: 31121365]
[http://dx.doi.org/10.1084/jem.20190418] [PMID: 31611251]
[http://dx.doi.org/10.1053/gast.1997.v113.pm9247454] [PMID: 9247454]
[http://dx.doi.org/10.1053/gast.2000.20229] [PMID: 11113068]
[http://dx.doi.org/10.1136/gut.49.1.42] [PMID: 11413109]
[http://dx.doi.org/10.1053/gast.2000.20196] [PMID: 11113067]
[http://dx.doi.org/10.1016/j.cgh.2006.03.028] [PMID: 16716759]
[PMID: 25438467]
[http://dx.doi.org/10.4049/jimmunol.1800697] [PMID: 30598515]
[http://dx.doi.org/10.1002/1521-4141(2000)30:8<2344::AID-IMMU2344>3.0.CO;2-7] [PMID: 10940925]
[http://dx.doi.org/10.1016/j.neuropharm.2014.10.020] [PMID: 25446571]
[http://dx.doi.org/10.1517/13543784.9.1.95] [PMID: 11060663]
[http://dx.doi.org/10.15761/JIC.1000102]
[http://dx.doi.org/10.4049/jimmunol.1601192] [PMID: 27543665]
[http://dx.doi.org/10.1016/S0009-9236(97)90065-5] [PMID: 9284853]
[http://dx.doi.org/10.1038/sj.gt.3301691] [PMID: 11973633]
[http://dx.doi.org/10.1016/j.cyto.2014.10.031] [PMID: 25481648]