Generic placeholder image

Current Vascular Pharmacology


ISSN (Print): 1570-1611
ISSN (Online): 1875-6212

Review Article

Interleukin-10 in the Vasculature: Pathophysiological Implications

Author(s): Raiany A. de Freitas, Victor V. Lima, Gisele F. Bomfim and Fernanda R.C. Giachini*

Volume 20, Issue 3, 2022

Published on: 01 March, 2022

Page: [230 - 243] Pages: 14

DOI: 10.2174/1570161120666211227143459

Price: $65


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.

Fiorentino DF, Bond MW, Mosmann TR. Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med 1989; 170(6): 2081-95.
[] [PMID: 2531194]
Ouyang W, O’Garra A. IL-10 family cytokines IL-10 and IL-22: From basic science to clinical translation. Immunity 2019; 50(4): 871-91.
[] [PMID: 30995504]
Sabat R. IL-10 family of cytokines. Cytokine Growth Factor Rev 2010; 21(5): 315-24.
[] [PMID: 21112807]
Burmeister AR, Marriott I. The interleukin-10 family of cytokines and their role in the CNS. Front Cell Neurosci 2018; 12: 458.
[] [PMID: 30542269]
Commins S, Steinke JW, Borish L. The extended IL-10 superfamily: IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, IL-28, and IL-29. J Allergy Clin Immunol 2008; 121(5): 1108-11.
[] [PMID: 18405958]
Ouyang W, Rutz S, Crellin NK, Valdez PA, Hymowitz SG. Regulation and functions of the IL-10 family of cytokines in inflammation and disease. Annu Rev Immunol 2011; 29: 71-109.
[] [PMID: 21166540]
Sziksz E, Pap D, Lippai R, et al. Fibrosis related inflammatory mediators: Role of the IL-10 cytokine family. Mediators Inflamm 2015; 2015: 764641.
[] [PMID: 26199463]
Finbloom DS, Winestock KD. IL-10 induces the tyrosine phosphorylation of tyk2 and Jak1 and the differential assembly of STAT1 alpha and STAT3 complexes in human T cells and monocytes. J Immunol 1995; 155(3): 1079-90.
[PMID: 7543512]
Deng G, Li K, Chen S, et al. Interleukin-10 promotes proliferation and migration, and inhibits tendon differentiation via the JAK/Stat3 pathway in tendon-derived stem cells in vitro. Mol Med Rep 2018; 18(6): 5044-52.
[] [PMID: 30320384]
Riley JK, Takeda K, Akira S, Schreiber RD. Interleukin-10 receptor signaling through the JAK-STAT pathway. Requirement for two distinct receptor-derived signals for anti-inflammatory action. J Biol Chem 1999; 274(23): 16513-21.
[] [PMID: 10347215]
Harhous Z, Booz GW, Ovize M, Bidaux G, Kurdi M. An update on the multifaceted roles of STAT3 in the heart. Front Cardiovasc Med 2019; 6: 150.
[] [PMID: 31709266]
Hillmer EJ, Zhang H, Li HS, Watowich SS. STAT3 signaling in immunity. Cytokine Growth Factor Rev 2016; 31: 1-15.
[] [PMID: 27185365]
Hutchins AP, Diez D, Miranda-Saavedra D. The IL-10/STAT3-mediated anti-inflammatory response: Recent developments and future challenges. Brief Funct Genomics 2013; 12(6): 489-98.
[] [PMID: 23943603]
Harrison DA. The Jak/STAT pathway. Cold Spring Harb Perspect Biol 2012; 4(3): a011205.
[] [PMID: 22383755]
Murray PJ. The JAK-STAT signaling pathway: Input and output integration. J Immunol 2007; 178(5): 2623-9.
[] [PMID: 17312100]
Pedroso JAB, Ramos-Lobo AM, Donato J Jr. SOCS3 as a future target to treat metabolic disorders. Hormones (Athens) 2019; 18(2): 127-36.
[] [PMID: 30414080]
Carow B, Rottenberg ME. SOCS3, a major regulator of infection and inflammation. Front Immunol 2014; 5: 58.
[] [PMID: 24600449]
Dela Justina V, San Martin S, López-Espíndola D, et al. Increased expression of STAT3 and SOCS3 in placenta from hyperglycemic rats. Eur J Histochem 2019; 63(4)
[] [PMID: 31833328]
Cevey ÁC, Penas FN, Alba Soto CD, Mirkin GA, Goren NB. IL-10/STAT3/SOCS3 axis is involved in the anti-inflammatory effect of benznidazole. Front Immunol 2019; 10: 1267.
[] [PMID: 31214200]
Murray PJ. Understanding and exploiting the endogenous interleukin-10/STAT3-mediated anti-inflammatory response. Curr Opin Pharmacol 2006; 6(4): 379-86.
[] [PMID: 16713356]
Babon JJ, Varghese LN, Nicola NA. Inhibition of IL-6 family cytokines by SOCS3. Semin Immunol 2014; 26(1): 13-9.
[] [PMID: 24418198]
Sarvas LJ. The IL-6 paradox: Context dependent interplay of SOCS3 and AMPK. J Diabetes Metab 2013; 01
Bagchi AK, Sharma A, Akolkar G, Singal PK. Crosstalk between toll-like receptor 4 and interleukin 10 in cardiomyocyte survival. FASEB J 2013; 27: 1128.5.
Shi J, Wang H, Guan H, et al. IL10 inhibits starvation-induced autophagy in hypertrophic scar fibroblasts via cross talk between the IL10-IL10R-STAT3 and IL10-AKT-mTOR pathways. Cell Death Dis 2016; 7: e2133.
[] [PMID: 26962683]
Freitas RA, Junior RRP, Justina VD, et al. Angiotensin (1-7)-attenuated vasoconstriction is associated with the Interleukin-10 signaling pathway. Life Sci 2020; 262: 118552.
[] [PMID: 33035583]
Miguez JSG, Dela Justina V, Bressan AFM, et al. O-Glycosylation with O-linked β-N-acetylglucosamine increases vascular contraction: Possible modulatory role on Interleukin-10 signaling pathway. Life Sci 2018; 209: 78-84.
[] [PMID: 30075176]
Noble KE, Harkness D, Yong KL. Interleukin 10 regulates cellular responses in monocyte/endothelial cell co-cultures. Br J Haematol 2000; 108(3): 497-504.
[] [PMID: 10759705]
Chen CC, Manning AM. TGF-β 1, IL-10 and IL-4 differentially modulate the cytokine-induced expression of IL-6 and IL-8 in human endothelial cells. Cytokine 1996; 8(1): 58-65.
[] [PMID: 8742067]
Kassan M, Galan M, Partyka M, Trebak M, Matrougui K. Interleukin-10 released by CD4(+)CD25(+) natural regulatory T cells improves microvascular endothelial function through inhibition of NADPH oxidase activity in hypertensive mice. Arterioscler Thromb Vasc Biol 2011; 31(11): 2534-42.
[] [PMID: 21817097]
Saraiva M, O’Garra A. The regulation of IL-10 production by immune cells. Nat Rev Immunol 2010; 10(3): 170-81.
[] [PMID: 20154735]
Kumar RK, Kaiser LM, Rockwell CE, Watts SW. Interleukin-10 does not contribute to the anti-contractile nature of PVAT in health. Vascul Pharmacol 2021; 138: 106838.
[] [PMID: 33540122]
Mosser DM, Zhang X. Interleukin-10: New perspectives on an old cytokine. Immunol Rev 2008; 226: 205-18.
[] [PMID: 19161426]
Bakiri AH, Mingomataj EÇ. Novel insights on interleukin-10 functions: A manipulative tool for the deviation of immune response and disease outcome. Eur Med J 2019; 4: 88-94.
Zimmerman MA, Reznikov LL, Raeburn CD, Selzman CH. Interleukin-10 attenuates the response to vascular injury. J Surg Res 2004; 121(2): 206-13.
[] [PMID: 15501460]
Matsumoto M, Fujii Y, Baba A, Hikida M, Kurosaki T, Baba Y. The calcium sensors STIM1 and STIM2 control B cell regulatory function through interleukin-10 production. Immunity 2011; 34(5): 703-14.
[] [PMID: 21530328]
Baba Y, Matsumoto M, Kurosaki T. Calcium signaling in B cells: Regulation of cytosolic Ca2+ increase and its sensor molecules, STIM1 and STIM2. Mol Immunol 2014; 62(2): 339-43.
[] [PMID: 24246800]
Mohanty S, Barik P, Debata N, Nagarajan P, Devadas S. iCa2+ Flux, ROS and IL-10 determines cytotoxic, and suppressor T cell functions in chronic human viral infections. Front Immunol 2020; 11: 83.
[] [PMID: 32210950]
Turovsky EA, Turovskaya MV, Gaidin SG, Zinchenko VP. Cytokine IL-10, activators of PI3-kinase, agonists of α-2 adrenoreceptor and antioxidants prevent ischemia-induced cell death in rat hippocampal cultures. Arch Biochem Biophys 2017; 615: 35-43.
[] [PMID: 28063948]
Eddie IP WK, Hoshi N, Shouval DS, Snapper S, Medzhitov R. Anti-inflammatory effect of IL-10 mediated by metabolic reprogramming of macrophages. Sec 2017; 356: 513-9.
Chen S, Kapturczak MH, Wasserfall C, et al. Interleukin 10 attenuates neointimal proliferation and inflammation in aortic allografts by a heme oxygenase-dependent pathway. Proc Natl Acad Sci USA 2005; 102(20): 7251-6.
[] [PMID: 15878989]
Krishnamurthy P, Rajasingh J, Lambers E, Qin G, Losordo DW, Kishore R. IL-10 inhibits inflammation and attenuates left ventricular remodeling after myocardial infarction via activation of STAT3 and suppression of HuR. Circ Res 2009; 104(2): e9-e18.
[] [PMID: 19096025]
Mazighi M, Pellé A, Gonzalez W, Mtairag EM, Philippe M, Hénin D, et al. IL-10 inhibits vascular smooth muscle cell activation in vitro and in vivo. Am J Physiol - Hear Circ Physiol 2004; 287.
Sung SA, Ko GJ, Jo SK, Cho WY, Kim HK, Lee SY. Interleukin-10 and tumor necrosis factor-α polymorphisms in vascular access failure in patients on hemodialysis: Preliminary data in Korea. J Korean Med Sci 2008; 23(1): 89-93.
[] [PMID: 18303205]
Lima VV, Zemse SM, Chiao CW, et al. Interleukin-10 limits increased blood pressure and vascular RhoA/Rho-kinase signaling in angiotensin II-infused mice. Life Sci 2016; 145: 137-43.
[] [PMID: 26682936]
Nomoto T, Okada T, Shimazaki K, et al. Systemic delivery of IL-10 by an AAV vector prevents vascular remodeling and end-organ damage in stroke-prone spontaneously hypertensive rat. Gene Ther 2009; 16(3): 383-91.
[] [PMID: 18818668]
Londoño D, Carvajal J, Strle K, Kim KS, Cadavid D. IL-10 Prevents apoptosis of brain endothelium during bacteremia. J Immunol 2011; 186(12): 7176-86.
[] [PMID: 21602495]
Liu H, Yang S, Sun X, Chen T. Human interleukin-10 gene inhibits acute rejection by triggering apoptosis in allograft vascular transplantation. Int J Clin Exp Pathol 2014; 7(9): 5864-71.
[PMID: 25337228]
Galeazzi M, Baldi C, Prisco E, et al. A Phase Ib clinical trial with F8-IL10, an anti-inflammatory immunocytokine for the treatment of rheumatoid arthritis (RA), used in combination with methotrexate. MTX 2012; pp. 1291-1.
Ersoy E, Kuş CNS, Şener U, Çoker I, Zorlu Y. The effects of interferon-β on interleukin-10 in multiple sclerosis patients. Eur J Neurol 2005; 12(3): 208-11.
[] [PMID: 15693810]
Traupe H. Psoriasis and the interleukin-10 family: Evidence for a protective genetic effect, but not an easy target as a drug. Br J Dermatol 2017; 176(6): 1438-9.
[] [PMID: 28581220]
Massey EJ, Sundstedt A, Day MJ, Corfield G, Anderton S, Wraith DC. Intranasal peptide-induced peripheral tolerance: The role of IL-10 in regulatory T cell function within the context of experimental autoimmune encephalomyelitis. Vet Immunol Immunopathol 2002; 87: 357-72.
Bomfim GF, Cau SBA, Bruno AS, Fedoce AG, Carneiro FS. Hypertension: A new treatment for an old disease? Targeting the immune system. Br J Pharmacol 2019; 176(12): 2028-48.
[] [PMID: 29969833]
McCarthy CG, Saha P, Golonka RM, Wenceslau CF, Joe B, Vijay-Kumar M. Innate immune cells and hypertension: Neutrophils and neutrophil extracellular traps (nets). Compr Physiol 2021; 11(1): 1575-89.
[] [PMID: 33577121]
Bomfim GF, Rodrigues FL, Carneiro FS. Are the innate and adaptive immune systems setting hypertension on fire? Pharmacol Res 2017; 117: 377-93.
[] [PMID: 28093357]
Kuriyama H, Ito Y, Suzuki H. Factors modifying contraction-relaxation cycle in vascular smooth muscles. Am Physiol Soc 1982; 12: 641e657.
Sweeney HL, Hammers DW. Muscle contraction. Cold Spring Harb Perspect Biol 2018; 10(2): a023200.
[] [PMID: 29419405]
Touyz RM, Alves-Lopes R, Rios FJ, et al. Vascular smooth muscle contraction in hypertension. Cardiovasc Res 2018; 114(4): 529-39.
[] [PMID: 29394331]
Webb RC. Smooth muscle contraction and relaxation. Adv Physiol Educ 2003; 27(1-4): 201-6.
[] [PMID: 14627618]
Brozovich FV, Nicholson CJ, Degen CV, Gao YZ, Aggarwal M, Morgan KG. Mechanisms of vascular smooth muscle contraction and the basis for pharmacologic treatment of smooth muscle disorders. Pharmacol Rev 2016; 68(2): 476-532.
[] [PMID: 27037223]
Giachini FRC, Zemse SM, Carneiro FS, et al. Interleukin-10 attenuates vascular responses to endothelin-1 via effects on ERK1/2-dependent pathway. Am J Physiol Heart Circ Physiol 2009; 296(2): H489-96.
[] [PMID: 19074677]
Keubler LM, Buettner M, Häger C, Bleich A. A multihit model: Colitis lessons from the interleukin-10-deficient mouse. Inflamm Bowel Dis 2015; 21(8): 1967-75.
[] [PMID: 26164667]
Gunnett CA, Heistad DD, Berg DJ, Faraci FM, Carol A, Heistad DD, et al. IL-10 deficiency increases superoxide and endothelial dysfunction during inflammation. Am J Physiol Heart Circ Physiol 2000; 279(4): H1555-62.
[] [PMID: 11009441]
Mutlak M, Kehat I. Extracellular signal-regulated kinases 1/2 as regulators of cardiac hypertrophy. Front Pharmacol 2015; 6: 149.
[] [PMID: 26257652]
Sano M, Fukuda K, Sato T, et al. ERK and p38 MAPK, but not NF-kappaB, are critically involved in reactive oxygen species-mediated induction of IL-6 by angiotensin II in cardiac fibroblasts. Circ Res 2001; 89(8): 661-9.
[] [PMID: 11597988]
Krymsky MA, Chibalina MV, Shirinsky VP, Marston SB, Vorotnikov AV. Evidence against the regulation of caldesmon inhibitory activity by p42/p44erk mitogen-activated protein kinase in vitro and demonstration of another caldesmon kinase in intact gizzard smooth muscle. FEBS Lett 1999; 452(3): 254-8.
[] [PMID: 10386601]
Sousa-Lopes A, de Freitas RA, Carneiro FS, et al. Angiotensin (1-7) inhibits Ang II-mediated ERK1/2 activation by stimulating MKP-1 activation in vascular smooth muscle cells. Int J Mol Cell Med 2020; 9(1): 50-61.
[] [PMID: 32832484]
Gary-Gouy H, Harriague J, Bismuth G, Platzer C, Schmitt C, Dalloul AH. Human CD5 promotes B-cell survival through stimulation of autocrine IL-10 production. Blood 2002; 100(13): 4537-43.
[] [PMID: 12393419]
Hammer M, Mages J, Dietrich H, et al. Control of dual-specificity phosphatase-1 expression in activated macrophages by IL-10. Eur J Immunol 2005; 35(10): 2991-3001.
[] [PMID: 16184516]
Bressan AF, Fonseca GA, Tostes RC, Webb RC, et al. Interleukin-10 negatively modulates extracellular signal-regulated kinase 1 and 2 in aorta from hypertensive mouse induced by angiotensin II infusion. Fundain Clin Pharmacol 2019; 33(1): 31-40.
Giachini FR, Sullivan JC, Lima VV, et al. IASH - ERK1/2 activation, via dowregulation of MKP-1, mediates sex-differences in doca-salt hypertension vascular reactivity. Hypertension 2010; 55: 172-9.
[] [PMID: 19901158]
Bressan AF, Fonseca GA, Tostes RC, Webb RC, Vitorino V, Regina F. Interleukin-10 negatively modulates extracellular signal-regulated kinases 1 and 2 in aorta from hypertensive mouse induced by angiotensin II infusion. 2019; 31-40.
Kwon WY, Cha HN, Heo JY, et al. Interleukin-10 deficiency aggravates angiotensin II-induced cardiac remodeling in mice. Life Sci 2016; 146: 214-21.
[] [PMID: 26775566]
Clark JF, Pyne-Geithman G. Vascular smooth muscle function: The physiology and pathology of vasoconstriction. Pathophysiology 2005; 12(1): 35-45.
[] [PMID: 15927823]
Szasz T, Webb RC. Rho-mancing to sensitize calcium signaling for contraction in the vasculature: Role of rho kinase. Adv Pharmacol 2017; 78: 303-22.
Agabiti-Rosei C, Paini A, De Ciuceis C, et al. Modulation of vascular reactivity by perivascular adipose tissue (PVAT). Curr Hypertens Rep 2018; 20(5): 44.
[] [PMID: 29736674]
Pohl U, Holtz J, Busse R, Bassenge E. Crucial role of endothelium in the vasodilator response to increased flow in vivo. Hypertension 1986; 8(1): 37-44.
[] [PMID: 3080370]
Casey DP, Walker BG, Ranadive SM, Taylor JL, Joyner MJ. Contribution of nitric oxide in the contraction-induced rapid vasodilation in young and older adults. J Appl Physiol 2013; 115(4): 446-55.
[] [PMID: 23788575]
Andrew PJ, Mayer B. Enzymatic function of nitric oxide synthases. Cardiovasc Res 1999; 43(3): 521-31.
[] [PMID: 10690324]
Jones SP, Greer JJM, Kakkar AK, et al. Endothelial nitric oxide synthase overexpression attenuates myocardial reperfusion injury. Am J Physiol-Hear Circ Physiol 2004; 286: 276-82.
Konukoglu D, Uzun H. Endothelial dysfunction and hypertension. Adv Exp Med Biol 2017; 956: 511-40.
[] [PMID: 28035582]
Didion SP, Kinzenbaw DA, Schrader LI, Chu Y, Faraci FM. Endogenous interleukin-10 inhibits angiotensin II-induced vascular dysfunction. Hypertension 2009; 54(3): 619-24.
[] [PMID: 19620507]
Singh P, Castillo A, Islam MT, Majid DSA. Evidence for prohypertensive, proinflammatory effect of interleukin-10 during chronic high salt intake in the condition of elevated angiotensin II level. Hypertension 2017; 70(4): 839-45.
[] [PMID: 28847894]
Zemse SM, Hilgers RH, Simkins GB, Rudic RD, Webb RC. Restoration of endothelin-1-induced impairment in endothelium-dependent relaxation by interleukin-10 in murine aortic rings. Can J Physiol Pharmacol 2008; 86(8): 557-65.
[] [PMID: 18758504]
Fichtlscherer S, Breuer S, Heeschen C, Dimmeler S, Zeiher AM. Interleukin-10 serum levels and systemic endothelial vasoreactivity in patients with coronary artery disease. J Am Coll Cardiol 2004; 44(1): 44-9.
[] [PMID: 15234404]
Gunnett CA, Lund DD, Faraci FM, Heistad DD. Vascular interleukin-10 protects against LPS-induced vasomotor dysfunction. Am J Physiol-Hear Circ Physiol 2005; 289.
Robertson SA, Skinner RJ, Care AS. Essential role for IL-10 in resistance to lipopolysaccharide-induced preterm labor in mice. J Immunol 2006; 177(7): 4888-96.
[] [PMID: 16982931]
de Vries JE. Immunosuppressive and anti-inflammatory properties of interleukin 10. Ann Med 1995; 27(5): 537-41.
[] [PMID: 8541028]
Adam M, Kooreman NG, Jagger A, et al. Systemic upregulation of IL-10 (interleukin-10) using a nonimmunogenic vector reduces growth and rate of dissecting abdominal aortic aneurysm. Arterioscler Thromb Vasc Biol 2018; 38(8): 1796-805.
[] [PMID: 29880489]
Myers DD Jr, Hawley AE, Farris DM, et al. Cellular IL-10 is more effective than viral IL-10 in decreasing venous thrombosis. J Surg Res 2003; 112(2): 168-74.
[] [PMID: 12888334]
Nonaka-Sarukawa M, Okada T, Ito T, et al. Adeno-associated virus vector-mediated systemic interleukin-10 expression ameliorates hypertensive organ damage in Dahl salt-sensitive rats. J Gene Med 2008; 10(4): 368-74.
[] [PMID: 18205252]
Ito T, Okada T, Miyashita H, et al. Interleukin-10 expression mediated by an adeno-associated virus vector prevents monocrotaline-induced pulmonary arterial hypertension in rats. Circ Res 2007; 101(7): 734-41.
[] [PMID: 17673672]
Mu W, Ouyang X, Agarwal A, et al. IL-10 suppresses chemokines, inflammation, and fibrosis in a model of chronic renal disease. J Am Soc Nephrol 2005; 16(12): 3651-60.
[] [PMID: 16251240]
Gillis EE, Musall JB, Baban B, Sullivan JC. IL-10 treatment decreases blood pressure in male, but not female, spontaneously hypertensive rats. Am J Physiol Renal Physiol 2020; 319(3): F359-65.
[] [PMID: 32686523]
Segiet A, Smykiewicz P, Kwiatkowski P, Żera T. Tumour necrosis factor and interleukin 10 in blood pressure regulation in spontaneously hypertensive and normotensive rats. Cytokine 2019; 113: 185-94.
[] [PMID: 30539780]
Tinsley JH, South S, Chiasson VL, Mitchell BM. Interleukin-10 reduces inflammation, endothelial dysfunction, and blood pressure in hypertensive pregnant rats. Am J Physiol Regul Integr Comp Physiol 2010; 298(3): R713-9.
[] [PMID: 20053959]
Rios FJ, Montezano AC, Touyz RM. Lessons learned from RAG-1-deficient mice in hypertension. Hypertension 2020; 75(4): 935-7.
[] [PMID: 32078397]
Ji H, Zheng W, Li X, et al. Sex-specific T-cell regulation of angiotensin II-dependent hypertension. Hypertension 2014; 64(3): 573-82.
[] [PMID: 24935938]
Gillis EE, Sullivan JC. Sex differences in hypertension: Recent advances. Hypertension 2016; 68(6): 1322-7.
[] [PMID: 27777357]
Belanger KM, Crislip GR, Gillis EE, et al. Greater T regulatory cells in females attenuate DOCA-salt-induced increases in blood pressure versus males. Hypertension 2020; 75(6): 1615-23.
[] [PMID: 32336228]
Sylvester MA, Brooks HL. Sex-specific mechanisms in inflammation and hypertension. Curr Hypertens Rep 2019; 21(7): 53.
[] [PMID: 31123838]
Kim HY, Cha HJ, Kim HS. CCL5 upregulates IL-10 expression and partially mediates the antihypertensive effects of IL-10 in the vascular smooth muscle cells of spontaneously hypertensive rats. Hypertens Res 2015; 38(10): 666-74.
[] [PMID: 25971630]
Kim HY, Kim HS. IL-10 up-regulates CCL5 expression in vascular smooth muscle cells from spontaneously hypertensive rats. Cytokine 2014; 68(1): 40-9.
[] [PMID: 24656930]
Yang Z, Zingarelli B, Szabó C. Crucial role of endogenous interleukin-10 production in myocardial ischemia/reperfusion injury. Circulation 2000; 101(9): 1019-26.
[] [PMID: 10704170]
Verma SK, Garikipati VNS, Krishnamurthy P, et al. IL-10 accelerates re-endothelialization and inhibits post-injury intimal hyperplasia following carotid artery denudation. PLoS One 2016; 11(1): e0147615.
[] [PMID: 26808574]
Krishnamurthy P, Thal M, Verma S, et al. Interleukin-10 deficiency impairs bone marrow-derived endothelial progenitor cell survival and function in ischemic myocardium. Circ Res 2011; 109(11): 1280-9.
[] [PMID: 21959218]
Wang Y, Fan L, Meng X, et al. Transplantation of IL-10-transfected endothelial progenitor cells improves retinal vascular repair via suppressing inflammation in diabetic rats. Graefes Arch Clin Exp Ophthalmol 2016; 254(10): 1957-65.
[] [PMID: 27405975]
McCarthy C, Duffy MM, Mooney D, et al. IL-10 mediates the immunoregulatory response in conjugated linoleic acid-induced regression of atherosclerosis. FASEB J 2013; 27(2): 499-510.
[] [PMID: 23070607]
Han X, Kitamoto S, Wang H, Boisvert WA. Interleukin-10 overexpression in macrophages suppresses atherosclerosis in hyperlipidemic mice. FASEB J 2010; 24(8): 2869-80.
[] [PMID: 20354139]
Kim H-J, Higashimori T, Park S-Y, et al. Differential effects of interleukin-6 and -10 on skeletal muscle and liver insulin action in vivo. Diabetes 2004; 53(4): 1060-7.
[] [PMID: 15047622]
Hong E-G, Ko HJ, Cho Y-R, et al. Interleukin-10 prevents diet-induced insulin resistance by attenuating macrophage and cytokine response in skeletal muscle. Diabetes 2009; 58(11): 2525-35.
[] [PMID: 19690064]
Gao M, Zhang C, Ma Y, Bu L, Yan L, Liu D. Hydrodynamic delivery of mIL10 gene protects mice from high-fat diet-induced obesity and glucose intolerance. Mol Ther 2013; 21(10): 1852-61.
[] [PMID: 23774795]
Blüher M. Obesity: global epidemiology and pathogenesis. Nat Rev Endocrinol 2019; 15(5): 288-98.
[] [PMID: 30814686]
Juge-Aubry CE, Somm E, Pernin A, et al. Adipose tissue is a regulated source of interleukin-10. Cytokine 2005; 29(6): 270-4.
[] [PMID: 15749027]
Akoumianakis I, Tarun A, Antoniades C. Perivascular adipose tissue as a regulator of vascular disease pathogenesis: Identifying novel therapeutic targets. Br J Pharmacol 2017; 174(20): 3411-24.
[] [PMID: 27976387]
Acosta JR, Tavira B, Douagi I, et al. Human-specific function of IL-10 in adipose tissue linked to insulin resistance. J Clin Endocrinol Metab 2019; 104(10): 4552-62.
[] [PMID: 31132124]
Seyed Jafari SM, Shafighi M, Beltraminelli H, et al. Efficacy of in vivo electroporation-mediated IL-10 gene delivery on survival of skin flaps. J Membr Biol 2018; 251(2): 211-9.
[] [PMID: 28776087]
McInnes IB, Illei GG, Danning CL, et al. IL-10 improves skin disease and modulates endothelial activation and leukocyte effector function in patients with psoriatic arthritis. J Immunol 2001; 167(7): 4075-82.
[] [PMID: 11564829]
Tang TT, Wang B, Wu M, et al. Extracellular vesicle-encapsulated IL-10 as novel nanotherapeutics against ischemic AKI. Sci Adv 2020; 6(33): eaaz0748.
[] [PMID: 32851154]
Shamskhou EA, Kratochvil MJ, Orcholski ME, et al. Hydrogel-based delivery of Il-10 improves treatment of bleomycin-induced lung fibrosis in mice. Biomaterials 2019; 203: 52-62.
[] [PMID: 30852423]
Fourman LT, Saylor CF, Cheru L, et al. Anti-inflammatory interleukin 10 inversely relates to coronary atherosclerosis in persons with human immunodeficiency virus. J Infect Dis 2020; 221(4): 510-5.
[] [PMID: 31077265]
Heeschen C, Dimmeler S, Hamm CW, et al. Serum level of the antiinflammatory cytokine interleukin-10 is an important prognostic determinant in patients with acute coronary syndromes. Circulation 2003; 107(16): 2109-14.
[] [PMID: 12668510]
Mittal SK, Roche PA. Suppression of antigen presentation by IL-10. Curr Opin Immunol 2015; 34: 22-7.
[] [PMID: 25597442]
Caligiuri G, Rudling M, Ollivier V, et al. Interleukin-10 deficiency increases atherosclerosis, thrombosis, and low-density lipoproteins in apolipoprotein E knockout mice. Mol Med 2003; 9(1-2): 10-7.
[] [PMID: 12765335]
Chernoff AE, Granowitz EV, Shapiro L, et al. A randomized, controlled trial of IL-10 in humans. Inhibition of inflammatory cytokine production and immune responses. J Immunol 1995; 154(10): 5492-9.
[PMID: 7730651]
Schwager K, Kaspar M, Bootz F, et al. Preclinical characterization of DEKAVIL (F8-IL10), a novel clinical-stage immunocytokine which inhibits the progression of collagen-induced arthritis. Arthritis Res Ther 2009; 11(5): R142.
[] [PMID: 19781067]
Llorente L, Richaud-Patin Y, García-Padilla C, et al. Clinical and biologic effects of anti-interleukin-10 monoclonal antibody administration in systemic lupus erythematosus. Arthritis Rheum 2000; 43(8): 1790-800.
[<1790::AID-ANR15>3.0.CO;2-2] [PMID: 10943869]
Roberti ML, Ricottini L, Capponi A, et al. Immunomodulating treatment with low dose interleukin-4, interleukin-10 and interleukin-11 in psoriasis vulgaris. J Biol Regul Homeost Agents 2014; 28(1): 133-9.
[PMID: 24750799]
Lindsay JO, Hodgson HJF. Review article: The immunoregulatory cytokine interleukin-10--a therapy for Crohn’s disease? Aliment Pharmacol Ther 2001; 15(11): 1709-16.
[] [PMID: 11683684]
Bickston SJ, Cominelli F. Recombinant interleukin 10 for the treatment of active Crohn’s disease: Lessons in biologic therapy. Gastroenterology 2000; 119(6): 1781-3.
[] [PMID: 11113101]
Autio K, Oft M. Pegylated interleukin-10: Clinical development of an immunoregulatory cytokine for use in cancer therapeutics. Curr Oncol Rep 2019; 21(2): 19.
[] [PMID: 30790069]
Ribeiro F, Alves AJ, Teixeira M, et al. Exercise training increases interleukin-10 after an acute myocardial infarction: A randomised clinical trial. Int J Sports Med 2012; 33(3): 192-8.
[] [PMID: 22187388]
Aghaei Bahmanbeglou N, Ebrahim K, Maleki M, Nikpajouh A, Ahmadizad S. Short-duration high-intensity interval exercise training is more effective than long duration for blood pressure and arterial stiffness but not for inflammatory markers and lipid profiles in patients with stage 1 hypertension. J Cardiopulm Rehabil Prev 2019; 39(1): 50-5.
[] [PMID: 30586113]
Gotsman I, Stabholz A, Planer D, et al. Serum cytokine tumor necrosis factor-alpha and interleukin-6 associated with the severity of coronary artery disease: Indicators of an active inflammatory burden? Isr Med Assoc J 2008; 10(7): 494-8.
[PMID: 18751625]
Tang JN, Shen DL, Liu CL, et al. Plasma levels of C1q/TNF-related protein 1 and interleukin 6 in patients with acute coronary syndrome or stable angina pectoris. Am J Med Sci 2015; 349(2): 130-6.
[] [PMID: 25635749]
Amin MN, Siddiqui SA, Ibrahim M, et al. Inflammatory cytokines in the pathogenesis of cardiovascular disease and cancer. SAGE Open Med 2020; 8: 2050312120965752.
[] [PMID: 33194199]
Dan K, Gomi S, Inokuchi K, et al. Effects of interleukin-1 and tumor necrosis factor on megakaryocytopoiesis: Mechanism of reactive thrombocytosis. Acta Haematol 1995; 93(2-4): 67-72.
[] [PMID: 7639054]
Ertenli I, Kiraz S, Oztürk MA, Haznedaroğlu Ic, Celik I, Calgüneri M. Pathologic thrombopoiesis of rheumatoid arthritis. Rheumatol Int 2003; 23(2): 49-60.
[] [PMID: 12634936]
Sahin O, Sahin M, Turhan H. Essential thrombocytosis manifested as myocardial infarction and congestive heart failure: Two case reports. Acta Cardiol 2005; 60(6): 651-2.
[] [PMID: 16385927]
Gaman AM, Moisa C, Diaconu CC, Gaman MA. Crosstalk between oxidative stress, chronic inflammation and disease progression in essential thrombocythemia. Rev Chim 2019; 70: 3486-9.
Schafer AI. Thrombocytosis. N Engl J Med 2004; 350(12): 1211-9.
[] [PMID: 15028825]
Kaser A, Brandacher G, Steurer W, et al. Interleukin-6 stimulates thrombopoiesis through thrombopoietin: Role in inflammatory thrombocytosis. Blood 2001; 98(9): 2720-5.
[] [PMID: 11675343]
Ertenli I, Haznedaroğlu IC, Kiraz S, Celik I, Calgüneri M, Kirazhi S. Cytokines affecting megakaryocytopoiesis in rheumatoid arthritis with thrombocytosis. Rheumatol Int 1996; 16(1): 5-8.
[] [PMID: 8783415]
Barcelos ALV, de Oliveira EA, Haute GV, et al. Association of IL-10 to coronary disease severity in patients with metabolic syndrome. Clin Chim Acta 2019; 495: 394-8.
[] [PMID: 31075237]
Esposito K, Pontillo A, Giugliano F, et al. Association of low interleukin-10 levels with the metabolic syndrome in obese women. J Clin Endocrinol Metab 2003; 88(3): 1055-8.
[] [PMID: 12629085]
Manigrasso MR, Ferroni P, Santilli F, et al. Association between circulating adiponectin and interleukin-10 levels in android obesity: Effects of weight loss. J Clin Endocrinol Metab 2005; 90(10): 5876-9.
[] [PMID: 16030165]
Leon-Cabrera S, Arana-Lechuga Y, Esqueda-León E, et al. Reduced systemic levels of IL-10 are associated with the severity of obstructive sleep apnea and insulin resistance in morbidly obese humans. Mediators Inflamm 2015; 2015: 493409.
[] [PMID: 25944984]
Calcaterra V, De Amici M, Klersy C, et al. Adiponectin, IL-10 and metabolic syndrome in obese children and adolescents. Acta Biomed 2009; 80(2): 117-23.
[PMID: 19848048]
Febbraio MA. Role of interleukins in obesity: Implications for metabolic disease. Trends Endocrinol Metab 2014; 25(6): 312-9.
[] [PMID: 24698032]
Kaur K, Sharma AK, Singal PK. Significance of changes in TNF-α and IL-10 levels in the progression of heart failure subsequent to myocardial infarction. Am J Physiol-Hear Circ Physiol 2006; 291: 106-13.
Waehre T, Halvorsen B, Damås JK, et al. Inflammatory imbalance between IL-10 and TNFalpha in unstable angina potential plaque stabilizing effects of IL-10. Eur J Clin Invest 2002; 32(11): 803-10.
[] [PMID: 12423320]
Afzal MS, Anjum S, Farooqi Z-U-R, Noreen M, Safi SZ, Ashraf M, et al. Influence of IL-10 polymorphism on the development of coronary artery disease in Pakistan. Asian Biomed 2012; 6: 159-65.
Weng KP, Hsieh KS, Hwang YT, et al. IL-10 polymorphisms are associated with coronary artery lesions in acute stage of Kawasaki disease. Circ J 2010; 74(5): 983-9.
[] [PMID: 20339193]
Nakamura J, Watanabe S, Kimura H, et al. Adeno-associated virus vector-mediated interleukin-10 induction prevents vascular inflammation in a murine model of kawasaki disease. Sci Rep 2018; 8(1): 7601.
[] [PMID: 29765083]
Buck DB, Ultee KHJ, Zettervall SL, et al. Transperitoneal versus retroperitoneal approach for open abdominal aortic aneurysm repair in the targeted vascular National Surgical Quality Improvement Program. J Vasc Surg 2016; 64(3): 585-91.
[] [PMID: 26994954]
Onorati F, Santarpino G, Tangredi G, et al. Intra-aortic balloon pump induced pulsatile perfusion reduces endothelial activation and inflammatory response following cardiopulmonary bypass. Eur J Cardiothorac Surg 2009; 35(6): 1012-9.
[] [PMID: 19211261]
Onorati F, Santini F, Menon T, et al. Leukocyte filtration of blood cardioplegia attenuates myocardial damage and inflammation. Eur J Cardiothorac Surg 2013; 43(1): 81-9.
[] [PMID: 22466697]
Yilmaz MI, Solak Y, Saglam M, et al. The relationship between IL-10 levels and cardiovascular events in patients with CKD. Clin J Am Soc Nephrol 2014; 9(7): 1207-16.
[] [PMID: 24789549]
Girndt M, Kaul H, Sester U, et al. Anti-inflammatory interleukin-10 genotype protects dialysis patients from cardiovascular events. Kidney Int 2002; 62(3): 949-55.
[] [PMID: 12164877]
Silva T, Fragoso YD, Destro Rodrigues MFS, et al. Effects of photobiomodulation on interleukin-10 and nitrites in individuals with relapsing-remitting multiple sclerosis - Randomized clinical trial. PLoS One 2020; 15(4): e0230551.
[] [PMID: 32255785]
Carvalho JL, Britto A, de Oliveira APL, et al. Beneficial effect of low-level laser therapy in acute lung injury after i-I/R is dependent on the secretion of IL-10 and independent of the TLR/MyD88 signaling. Lasers Med Sci 2017; 32(2): 305-15.
[] [PMID: 27924419]
Searing D, Zhang Y, Murphy JR, Hauk PJ, Goleva E,Leung DYM. Decreased serum vitamin D levels in children with asthma with increase corticosteroid usage. J Allergy (Cairo) 2011; 125: 995-1000.
Quante T, Ng YC, Ramsay EE, et al. Corticosteroids reduce IL-6 in ASM cells via up-regulation of MKP-1. Am J Respir Cell Mol Biol 2008; 39(2): 208-17.
[] [PMID: 18314542]
Giomarelli P, Scolletta S, Borrelli E, Biagioli B. Myocardial and lung injury after cardiopulmonary bypass: Role of interleukin (IL)-10. Ann Thorac Surg 2003; 76(1): 117-23.
[] [PMID: 12842524]
Zhang WR, Garg AX, Coca SG, et al. Plasma IL-6 and IL-10 concentrations predict AKI and long-term mortality in adults after cardiac surgery. J Am Soc Nephrol 2015; 26(12): 3123-32.
[] [PMID: 25855775]
Rasmussen R, Bache S, Stavngaard T, Møller K. Plasma Levels of IL-6, IL-8, IL-10, ICAM-1, VCAM-1, IFNγ, and TNFα are not associated with delayed cerebral ischemia, cerebral vasospasm, or clinical outcome in patients with subarachnoid hemorrhage. World Neurosurg 2019; 128: e1131-6.
[] [PMID: 31121365]
Saraiva M, Vieira P, O’Garra A. Biology and therapeutic potential of interleukin-10. J Exp Med 2020; 217(1): 1-19.
[] [PMID: 31611251]
van Deventer SJ, Elson CO, Fedorak RN. Multiple doses of intravenous interleukin 10 in steroid-refractory Crohn’s disease. Gastroenterology 1997; 113(2): 383-9.
[] [PMID: 9247454]
Fedorak RN, Gangl A, Elson CO, et al. Recombinant human interleukin 10 in the treatment of patients with mild to moderately active Crohn’s disease. The Interleukin 10 Inflammatory Bowel Disease Cooperative Study Group. Gastroenterology 2000; 119(6): 1473-82.
[] [PMID: 11113068]
Colombel JF, Rutgeerts P, Malchow H, et al. Interleukin 10 (Tenovil) in the prevention of postoperative recurrence of Crohn’s disease. Gut 2001; 49(1): 42-6.
[] [PMID: 11413109]
Schreiber S, Fedorak RN, Nielsen OH, et al. Safety and efficacy of recombinant human interleukin 10 in chronic active Crohn’s disease. Crohn’s Disease IL-10 Cooperative Study Group. Gastroenterology 2000; 119(6): 1461-72.
[] [PMID: 11113067]
Braat H, Rottiers P, Hommes DW, et al. A phase I trial with transgenic bacteria expressing interleukin-10 in Crohn’s disease. Clin Gastroenterol Hepatol 2006; 4(6): 754-9.
[] [PMID: 16716759]
Galeazzi M, Bazzichi L, Sebastiani GD, et al. A phase IB clinical trial with Dekavil (F8-IL10), an immunoregulatory ‘armed antibody’ for the treatment of rheumatoid arthritis, used in combination wiIh methotrexate. Isr Med Assoc J 2014; 16(10): 666.
[PMID: 25438467]
Mann EH, Gabryšová L, Pfeffer PE, O’Garra A, Hawrylowicz CM. High-dose IL-2 skews a glucocorticoid-driven IL-17+IL-10+ memory CD4+ T cell response towards a single IL-10-producing phenotype. J Immunol 2019; 202(3): 684-93.
[] [PMID: 30598515]
Richards DF, Fernandez M, Caulfield J, Hawrylowicz CM, Richards D. Glucocorticoids drive human CD8(+) T cell differentiation towards a phenotype with high IL-10 and reduced IL-4, IL-5 and IL-13 production. Eur J Immunol 2000; 30(8): 2344-54.
[<2344::AID-IMMU2344>3.0.CO;2-7] [PMID: 10940925]
Kwilasz AJ, Grace PM, Serbedzija P, Maier SF, Watkins LR. The therapeutic potential of interleukin-10 in neuroimmune diseases. Neuropharmacology 2015; 96(Pt A): 55-69.
[] [PMID: 25446571]
Asadullah K, Döcke WD, Sabat RV, Volk HD, Sterry W. The treatment of psoriasis with IL-10: Rationale and review of the first clinical trials. Expert Opin Investig Drugs 2000; 9(1): 95-102.
[] [PMID: 11060663]
Fioranelli M, Grazia RM. Twenty-five years of studies and trials for the therapeutic application of IL-10 immunomodulating properties. From high doses administration to low dose medicine new paradigm. Res Artic J Integr Cardiol J Integr Cardiol 2014.
Castillo P, Kolls JK. Cytokines IL-10: A paradigm for counterregulatory. J Immunol 2016; 197: 1529-35.
[] [PMID: 27543665]
Huhn RD, Radwanski E, Gallo J, et al. Pharmacodynamics of subcutaneous recombinant human interleukin-10 in healthy volunteers. Clin Pharmacol Ther 1997; 62(2): 171-80.
[] [PMID: 9284853]
Adachi O, Nakano A, Sato O, et al. Gene transfer of Fc-fusion cytokine by in vivo electroporation: Application to gene therapy for viral myocarditis. Gene Ther 2002; 9(9): 577-83.
[] [PMID: 11973633]
Saxena A, Khosraviani S, Noel S, Mohan D, Donner T, Hamad ARA. Interleukin-10 paradox: A potent immunoregulatory cytokine that has been difficult to harness for immunotherapy. Cytokine 2015; 74(1): 27-34.
[] [PMID: 25481648]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy