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Original Research

Th1/Th2 Balance in Young Subjects: Relationship with Cytokine Levels and Metabolic Profile

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Pages 6587-6600 | Published online: 06 Dec 2021

References

  • Donath MY, Shoelson SE. Type 2 diabetes as an inflammatory disease. Nat Rev Immunol. 2011;11(2):98–107. doi:10.1038/nri2925
  • Jung UJ, Choi MS. Obesity and its metabolic complications: the role of adipokines and the relationship between obesity, inflammation, insulin resistance, dyslipidemia and nonalcoholic fatty liver disease. Int J Mol Sci. 2014;15(4):6184–6223. doi:10.3390/ijms15046184
  • Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003;112(12):1796–1808. doi:10.1172/JCI19246
  • Wu H, Ballantyne CM. Metabolic inflammation and insulin resistance in obesity. Circ Res. 2020;126(11):1549–1564. doi:10.1161/CIRCRESAHA.119.315896
  • Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA. 2001;286(3):327–334. doi:10.1001/jama.286.3.327
  • Wegner M, Winiarska H, Bobkiewicz-Kozłowska T, Dworacka M. IL-12 serum levels in patients with type 2 diabetes treated with sulphonylureas. Cytokine. 2008;42(3):312–316. doi:10.1016/j.cyto.2008.02.014
  • Surendar J, Mohan V, Rao MM, Babu S, Aravindhan V. Increased levels of both Th1 and Th2 cytokines in subjects with metabolic syndrome (CURES-103). Diabetes Technol Ther. 2011;13(4):477–482. doi:10.1089/dia.2010.0178
  • Madhumitha H, Mohan V, Deepa M, Babu S, Aravindhan V. Increased Th1 and suppressed Th2 serum cytokine levels in subjects with diabetic coronary artery disease. Cardiovasc Diabetol. 2014;13:1. doi:10.1186/1475-2840-13-1
  • Zhou T, Hu Z, Yang S, Sun L, Yu Z, Wang G. Role of adaptive and innate immunity in type 2 diabetes mellitus. J Diabetes Res. 2018;2018:7457269. doi:10.1155/2018/7457269
  • Sell H, Eckel J. Adipose tissue inflammation: novel insight into the role of macrophages and lymphocytes. Curr Opin Clin Nutr Metab Care. 2010;13(4):366–370. doi:10.1097/MCO.0b013e32833aab7f
  • Feuerer M, Herrero L, Cipolletta D, et al. Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat Med. 2009;15(8):930–939. doi:10.1038/nm.2002
  • Nishimura S, Manabe I, Nagasaki M, et al. CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat Med. 2009;15(8):914–920. doi:10.1038/nm.1964
  • Winer S, Chan Y, Paltser G, et al. Normalization of obesity-associated insulin resistance through immunotherapy. Nat Med. 2009;15(8):921–929. doi:10.1038/nm.2001
  • Rocha VZ, Folco EJ, Sukhova G, et al. Interferon-gamma, a Th1 cytokine, regulates fat inflammation: a role for adaptive immunity in obesity. Circ Res. 2008;103(5):467–476. doi:10.1161/CIRCRESAHA.108.177105
  • Duffaut C, Zakaroff-Girard A, Bourlier V, et al. Interplay between human adipocytes and T lymphocytes in obesity: CCL20 as an adipochemokine and T lymphocytes as lipogenic modulators. Arterioscler Thromb Vasc Biol. 2009;29(10):1608–1614. doi:10.1161/ATVBAHA.109.192583
  • Kintscher U, Hartge M, Hess K, et al. T-lymphocyte infiltration in visceral adipose tissue: a primary event in adipose tissue inflammation and the development of obesity-mediated insulin resistance. Arterioscler Thromb Vasc Biol. 2008;28(7):1304–1310. doi:10.1161/ATVBAHA.108.165100
  • Hirahara K, Nakayama T. CD4+ T-cell subsets in inflammatory diseases: beyond the Th1/Th2 paradigm. Int Immunol. 2016;28(4):163–171. doi:10.1093/intimm/dxw006
  • McLaughlin T, Liu LF, Lamendola C, et al. T-cell profile in adipose tissue is associated with insulin resistance and systemic inflammation in humans. Arterioscler Thromb Vasc Biol. 2014;34(12):2637–2643. doi:10.1161/ATVBAHA.114.304636
  • Andersen CJ, Murphy KE, Fernandez ML. Impact of obesity and metabolic syndrome on immunity. Adv Nutr. 2016;7(1):66–75. doi:10.3945/an.115.010207
  • O’Rourke RW, Kay T, Scholz MH, et al. Alterations in T-cell subset frequency in peripheral blood in obesity. Obes Surg. 2005;15(10):1463–1468. doi:10.1381/096089205774859308
  • Kim JA, Park HS. White blood cell count and abdominal fat distribution in female obese adolescents. Metabolism. 2008;57(10):1375–1379. doi:10.1016/j.metabol.2008.05.005
  • Tanaka S, Isoda F, Ishihara Y, Kimura M, Yamakawa T. T lymphopaenia in relation to body mass index and TNF-alpha in human obesity: adequate weight reduction can be corrective. Clin Endocrinol. 2001;54(3):347–354.
  • Zhao R, Tang D, Yi S, et al. Elevated peripheral frequencies of Th22 cells: a novel potent participant in obesity and type 2 diabetes. PLoS One. 2014;9(1):e85770. doi:10.1371/journal.pone.0085770
  • Zeng C, Shi X, Zhang B, et al. The imbalance of Th17/Th1/Tregs in patients with type 2 diabetes: relationship with metabolic factors and complications. J Mol Med (Berl). 2012;90(2):175–186. doi:10.1007/s00109-011-0816-5
  • Upadhyay J, Farr O, Perakakis N, Ghaly W, Mantzoros C. Obesity as a disease. Med Clin North Am. 2018;102(1):13–33. doi:10.1016/j.mcna.2017.08.004
  • Saydah S, Bullard KM, Imperatore G, Geiss L, Gregg EW. Cardiometabolic risk factors among US adolescents and young adults and risk of early mortality. Pediatrics. 2013;131(3):e679–e686. doi:10.1542/peds.2012-2583
  • Alberti KG, Eckel RH, Grundy SM, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009;120(16):1640–1645. doi:10.1161/CIRCULATIONAHA.109.192644
  • Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412–419. doi:10.1007/BF00280883
  • Stentz FB, Kitabchi AE. Transcriptome and proteome expressions involved in insulin resistance in muscle and activated T-lymphocytes of patients with type 2 diabetes. Genomics Proteomics Bioinformatics. 2007;5(3–4):216–235. doi:10.1016/S1672-0229(08)60009-1
  • Guo H, Xu BC, Yang XG, et al. A high frequency of peripheral blood IL-22(+) CD4(+) T cells in patients with new onset type 2 diabetes mellitus. J Clin Lab Anal. 2016;30(2):95–102. doi:10.1002/jcla.21821
  • Zhao SL, Mo ZH, He HH, Zhao LL, Xie YH. Imbalance of T-helper 1/T-helper 2 cytokines and impaired glucose tolerance among patient with acute coronary syndrome. J Cancer Res Ther. 2018;14(9):S480–S485. doi:10.4103/0973-1482.194346
  • Pacifico L, Di Renzo L, Anania C, et al. Increased T-helper interferon-gamma-secreting cells in obese children. Eur J Endocrinol. 2006;154(5):691–697. doi:10.1530/eje.1.02138
  • Asadikaram G, Ram M, Izadi A, et al. The study of the serum level of IL-4, TGF-β, IFN-γ, and IL-6 in overweight patients with and without diabetes mellitus and hypertension. J Cell Biochem. 2019;120(3):4147–4157. doi:10.1002/jcb.27700
  • McGillicuddy FC, Chiquoine EH, Hinkle CC, et al. Interferon gamma attenuates insulin signaling, lipid storage, and differentiation in human adipocytes via activation of the JAK/STAT pathway. J Biol Chem. 2009;284(46):31936–31944. doi:10.1074/jbc.M109.061655
  • Cruz-Pineda WD, Parra-Rojas I, Rodríguez-Ruíz HA, Illades-Aguiar B, Matia-García I, Garibay-Cerdenares OL. The regulatory role of insulin in energy metabolism and leukocyte functions. J Leukoc Biol. 2021;1–12. doi:10.1002/JLB.2RU1220-847R
  • Viardot A, Heilbronn LK, Samocha-Bonet D, Mackay F, Campbell LV, Samaras K. Obesity is associated with activated and insulin resistant immune cells. Diabetes Metab Res Rev. 2012;28(5):447–454. doi:10.1002/dmrr.2302
  • Olson NC, Doyle MF, de Boer IH, et al. Associations of circulating lymphocyte subpopulations with type 2 diabetes: cross-sectional results from the multi-ethnic study of atherosclerosis (Mesa). PLoS One. 2015;10(10):e0139962. doi:10.1371/journal.pone.0139962
  • Sbierski-Kind J, Goldeck D, Buchmann N, et al. T cell phenotypes associated with insulin resistance: results from the Berlin aging study II. Immun Ageing. 2020;17(1):40. doi:10.1186/s12979-020-00211-y
  • Fischer HJ, Sie C, Schumann E, et al. The insulin receptor plays a critical role in T cell function and adaptive immunity. J Immunol. 2017;198(5):1910–1920. doi:10.4049/jimmunol.1601011
  • van der Weerd K, Dik WA, Schrijver B, et al. Morbidly obese human subjects have increased peripheral blood CD4+ T cells with skewing toward a Treg- and Th2-dominated phenotype. Diabetes. 2012;61(2):401–408. doi:10.2337/db11-1065
  • Bremer AA, Jialal I. Adipose tissue dysfunction in nascent metabolic syndrome. J Obes. 2013;2013:393192. doi:10.1155/2013/393192
  • Hotamisligil GS, Budavari A, Murray D, Spiegelman BM. Reduced tyrosine kinase activity of the insulin receptor in obesity-diabetes. Central role of tumor necrosis factor-alpha. J Clin Invest. 1994;94(4):1543–1549. doi:10.1172/JCI117495
  • Viardot A, Grey ST, Mackay F, Chisholm D. Potential antiinflammatory role of insulin via the preferential polarization of effector T cells toward a T helper 2 phenotype. Endocrinology. 2007;148(1):346–353. doi:10.1210/en.2006-0686
  • Tarantino G, Costantini S, Finelli C, et al. Is serum interleukin-17 associated with early atherosclerosis in obese patients? J Transl Med. 2014;12(1):214. doi:10.1186/s12967-014-0214-1
  • Feingold KR, Grunfeld C. Role of cytokines in inducing hyperlipidemia. Diabetes. 1992;41(Suppl 2):97–101. doi:10.2337/diab.41.2.s97
  • Mahlangu T, Dludla PV, Nyambuya TM, et al. A systematic review on the functional role of Th1/Th2 cytokines in type 2 diabetes and related metabolic complications. Cytokine. 2020;126:154892. doi:10.1016/j.cyto.2019.154892
  • Cosmi L, Maggi L, Santarlasci V, Liotta F, Annunziato F. T helper cells plasticity in inflammation. Cytometry A. 2014;85(1):36–42. doi:10.1002/cyto.a.22348
  • Sun Q, Li J, Gao F. New insights into insulin: the anti-inflammatory effect and its clinical relevance. World J Diabetes. 2014;5(2):89–96. doi:10.4239/wjd.v5.i2.89
  • Giri B, Dey S, Das T, Sarkar M, Banerjee J, Dash SK. Chronic hyperglycemia mediated physiological alteration and metabolic distortion leads to organ dysfunction, infection, cancer progression and other pathophysiological consequences: an update on glucose toxicity. Biomed Pharmacother. 2018;107:306–328. doi:10.1016/j.biopha.2018.07.157
  • Esposito K, Nappo F, Marfella R, et al. Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress. Circulation. 2002;106(16):2067–2072. doi:10.1161/01.cir.0000034509.14906.ae
  • Guha M, Bai W, Nadler JL, Natarajan R. Molecular mechanisms of tumor necrosis factor alpha gene expression in monocytic cells via hyperglycemia-induced oxidant stress-dependent and -independent pathways. J Biol Chem. 2000;275(23):17728–17739. doi:10.1074/jbc.275.23.17728
  • Arnalich F, Hernanz A, López-Maderuelo D, et al. Enhanced acute-phase response and oxidative stress in older adults with type II diabetes. Horm Metab Res. 2000;32(10):407–412. doi:10.1055/s-2007-978662
  • Vlassara H, Brownlee M, Manogue KR, Dinarello CA, Pasagian A. Cachectin/TNF and IL-1 induced by glucose-modified proteins: role in normal tissue remodeling. Science. 1988;240(4858):1546–1548. doi:10.1126/science.3259727
  • Stegenga ME, van der Crabben SN, Dessing MC, et al. Effect of acute hyperglycaemia and/or hyperinsulinaemia on proinflammatory gene expression, cytokine production and neutrophil function in humans. Diabet Med. 2008;25(2):157–164. doi:10.1111/j.1464-5491.2007.02348.x
  • Mirhafez SR, Ebrahimi M, Saberi Karimian M, et al. Serum high-sensitivity C-reactive protein as a biomarker in patients with metabolic syndrome: evidence-based study with 7284 subjects. Eur J Clin Nutr. 2016;70(11):1298–1304. doi:10.1038/ejcn.2016.111
  • Feingold KR, Grunfeld C. Tumor necrosis factor-alpha stimulates hepatic lipogenesis in the rat in vivo. J Clin Invest. 1987;80(1):184–190. doi:10.1172/JCI113046
  • Starnes HF Jr, Warren RS, Jeevanandam M, et al. Tumor necrosis factor and the acute metabolic response to tissue injury in man. J Clin Invest. 1988;82(4):1321–1325. doi:10.1172/JCI113733
  • Feingold KR, Soued M, Serio MK, Moser AH, Dinarello CA, Grunfeld C. Multiple cytokines stimulate hepatic lipid synthesis in vivo. Endocrinology. 1989;125(1):267–274. doi:10.1210/endo-125-1-267
  • Grunfeld C, Soued M, Adi S, et al. Interleukin 4 inhibits stimulation of hepatic lipogenesis by tumor necrosis factor, interleukin 1, and interleukin 6 but not by interferon-alpha. Cancer Res. 1991;51(11):2803–2807.
  • Juonala M, Viikari JS, Kähönen M, et al. Life-time risk factors and progression of carotid atherosclerosis in young adults: the cardiovascular risk in young Finns study. Eur Heart J. 2010;31(14):1745–1751. doi:10.1093/eurheartj/ehq141