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01-10-2017 | Original Article

Circulating IL-8 levels are increased in patients with type 2 diabetes and associated with worse inflammatory and cardiometabolic profile

Authors: F. A. Cimini, I. Barchetta, A. Porzia, F. Mainiero, C. Costantino, L. Bertoccini, V. Ceccarelli, S. Morini, M. G. Baroni, A. Lenzi, M. G. Cavallo

Published in: Acta Diabetologica | Issue 10/2017

Abstract

Aims

Interleukin-8 (IL-8) is a chemokine involved in systemic immunity, macrophages infiltration and activation in adipose tissue and may play a significant role in the pathogenesis of type 2 diabetes (T2D) and atherosclerosis. Aims of this study were to evaluate circulating IL-8 levels in adult patients with T2D in comparison with non-diabetic subjects and to describe clinical and biochemical correlates of IL-8 concentration.

Methods

For this cross-sectional study, we enrolled 79 consecutive T2D individuals referring to our diabetes outpatient clinics at Sapienza University of Rome, and 37 sex, age and BMI comparable non-diabetic subjects as a control group. Clinical parameters and medical history were recorded; fasting blood sampling was performed for biochemistry and for measuring serum IL-8, IL-6, TNF-α, CRP, adiponectin and 25(OH)vitamin D [25(OH)D] levels.

Results

Patients with T2D exhibited significantly higher serum IL-8 levels than non-diabetic subjects (69.27 ± 112.83 vs. 16.03 ± 24.27 pg/mL, p < 0.001). In diabetic patients, increased IL-8 concentration correlated with higher IL-6 (p < 0.001), TNF-α (p = 0.02), FBG (p = 0.035), HbA1c (p = 0.04) and LDL-C (p = 0.04) and with lower adiponectin (p = 0.02) and 25(OH)D (p = 0.003) concentrations.

Conclusions

Patients with T2D display a marked elevation of circulating IL-8 levels which identify subjects with worse inflammatory, glycometabolic and lipid profile and lower vitamin D levels. Further studies are warranted for evaluating a possible role of IL-8 as a novel marker for risk stratification in T2D patients.

Paniagua JA (2016) Nutrition, insulin resistance and dysfunctional adipose tissue determine the different components of metabolic syndrome. World J Diabetes 7:483–514CrossRefPubMedPubMedCentral

Lopes HF, Corrêa-Giannella ML, Consolim-Colombo FM, Egan BM (2016) Visceral adiposity syndrome. Diabetol Metab Syndr 8:40. doi:10.1186/s13098-016-0156-2 CrossRefPubMedPubMedCentral

Jung UJ, Choi MS (2014) 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 15:6184–6223. doi:10.3390/ijms15046184 CrossRefPubMedPubMedCentral

Chen L, Chen R, Wang H, Liang F (2015) Mechanisms linking inflammation to insulin resistance. Int J Endocrinol 2015:508409. doi:10.1155/2015/508409 PubMedPubMedCentral

Kammoun HL, Kraakman MJ, Febbraio MA (2014) Adipose tissue inflammation in glucose metabolism. Rev Endocr Metab Disord 15:31–44. doi:10.1007/s11154-013-9274-4 CrossRefPubMed

Alisi A, Carpino G, Oliveira FL, Panera N, Nobili V, Gaudio E (2017) The role of tissue macrophage-mediated inflammation on NAFLD pathogenesis and its clinical implications. Mediators Inflamm 2017:8162421. doi:10.1155/2017/8162421 CrossRefPubMedPubMedCentral

Nakamura K, Fuster JJ, Walsh K (2014) Adipokines: a link between obesity and cardiovascular disease. J Cardiol 63:250–259. doi:10.1016/j.jjcc.2013.11.006 CrossRefPubMed

Wensveen FM, Valentić S, Šestan M, Turk Wensveen T, Polić B (2015) The “Big Bang” in obese fat: events initiating obesity-induced adipose tissue inflammation. Eur J Immunol 45:2446–2456. doi:10.1002/eji.201545502 CrossRefPubMed

Kraakman MJ, Murphy AJ, Jandeleit-Dahm K, Kammoun HL (2014) Macrophage polarization in obesity and type 2 diabetes: weighing down our understanding of macrophage function? Front Immunol 5:470. doi:10.3389/fimmu.2014.00470 CrossRefPubMedPubMedCentral

10.

Meshkani R, Vakili S (2016) Tissue resident macrophages: key players in the pathogenesis of type 2 diabetes and its complications. Clin Chim Acta 462:77–89. doi:10.1016/j.cca.2016.08.015 CrossRefPubMed

11.

Blüher M (2016) Adipose tissue inflammation: a cause or consequence of obesity-related insulin resistance? Clin Sci 18:1603–1614. doi:10.1042/CS20160005 CrossRef

12.

Bastard JP, Maachi M, Lagathu C et al (2006) Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur Cytokine Netw 1:4–12

13.

Hotamisligil GS, Shargill NS, Spiegelman BM (1993) Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 5091:87–91CrossRef

14.

Calle MC, Fernandez ML (2012) Inflammation and type 2 diabetes. Diabetes Metab 38:183–191. doi:10.1016/j.diabet.2011.11.006 CrossRefPubMed

15.

Mirza S, Hossain M, Mathews C et al (2012) Type 2-diabetes is associated with elevated levels of TNF-alpha, IL-6 and adiponectin and low levels of leptin in a population of Mexican Americans: a cross-sectional study. Cytokine 1:136–142. doi:10.1016/j.cyto.2011.09.029 CrossRef

16.

Pickup JC, Chusney GD, Thomas SM, Burt D (2000) Plasma interleukin-6, tumour necrosis factor alpha and blood cytokine production in type 2 diabetes. Life Sci 67:291–300CrossRefPubMed

17.

Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM (2001) C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 286:327–334CrossRefPubMed

18.

Kim CS, Park HS, Kawada T et al (2006) Circulating levels of MCP-1 and IL-8 are elevated in human obese subjects and associated with obesity-related parameters. Int J Obes 9:1347–1355CrossRef

19.

Cavusoglu E, Marmur JD, Yanamadala S et al (2015) Elevated baseline plasma IL-8 levels are an independent predictor of long-term all-cause mortality in patients with acute coronary syndrome. Atherosclerosis 242:589–594. doi:10.1016/j.atherosclerosis.2015.08.022 CrossRefPubMed

20.

Ajmera V, Perito ER, Bass NM et al (2017) Novel plasma biomarkers associated with liver disease severity in adults with nonalcoholic fatty liver disease. Hepatology 65:65–77. doi:10.1002/hep.28776 CrossRefPubMed

21.

Mukaida N, Shiroo M, Matsushima K (1989) Genomic structure of the human monocyte-derived neutrophil chemotactic factor IL-8. J Immunol 143(4):1366–1371 PMID: 2663993 PubMed

22.

Remick DG (2005) Interleukin-8. Crit Care Med 33:S466–S467CrossRefPubMed

23.

Baggiolini M, Loetscher P, Moser B (1995) Interleukin-8 and the chemokine family. Int J Immunopharmacol 17:103–108CrossRefPubMed

24.

Leonard EJ, Yoshimura T (1990) Neutrophil attractant/activation protein-1 (NAP-1 [interleukin-8]). Am J Respir Cell Mol Biol 2(6):479–486 Review. PMID: 2189453 CrossRefPubMed

25.

Moreau M, Brocheriou I, Petit L, Ninio E, Chapman MJ, Rouis M (1999) Interleukin-8 mediates downregulation of tissue inhibitor of metalloproteinase-1 expression in cholesterol-loaded human macrophages: relevance to stability of atherosclerotic plaque. Circulation 99(3):420–426 PMID: 9918530 CrossRefPubMed

26.

Koch AE, Polverini PJ, Kunkel SL et al (1992) Interleukin-8 as a macrophage-derived mediator of angiogenesis. Science 258(5089):1798–1801 PMID: 1281554 CrossRefPubMed

27.

Yue TL, Mckenna PJ, Gu JL, Feuerstein GZ (1993) Interleukin-8 is chemotactic for vascular smooth muscle cells. Eur J Pharmacol 240(1):81–84 PMID: 8405125 CrossRefPubMed

28.

Gerszten RE, Garcia-Zepeda EA, Lim YC et al (1999) MCP-1 and IL-8 trigger firm adhesion of monocytes to vascular endothelium under flow conditions. Nature 398(6729):718–723 PMID: 10227295 CrossRefPubMed

29.

Joshi-Barve S, Barve SS, Butt W, Klein J, McClain CJ (2003) Inhibition of proteasome function leads to NF-kappaB-independent IL-8 expression in human hepatocytes. Hepatology 38(5):1178–1187 PubMed PMID: 14578856 CrossRefPubMed

30.

Zimmermann HW, Seidler S, Gassler N et al (2011) Interleukin-8 is activated in patients with chronic liver diseases and associated with hepatic macrophage accumulation in human liver fibrosis. PLoS ONE 6(6):e21381. doi:10.1371/journal.pone.0021381 Epub 2011 Jun 22. PubMed PMID: 21731723; PubMed Central PMCID: PMC3120868 CrossRefPubMedPubMedCentral

31.

Xu L, Kitade H, Ni Y, Ota T (2015) Roles of chemokines and chemokine receptors in obesity-associated insulin resistance and nonalcoholic fatty liver disease. Biomolecules 5(3):1563–1579. doi:10.3390/biom5031563 Review. PubMed PMID: 26197341; PubMed Central PMCID: PMC4598764 CrossRefPubMedPubMedCentral

32.

Mirza MS (2011) Obesity, visceral fat, and NAFLD: querying the role of adipokines in the progression of nonalcoholic fatty liver disease. ISRN Gastroenterol 2011:592404. doi: 10.5402/2011/592404. Epub 2011 Aug 28. PubMed PMID: 21991518; PubMed Central PMCID: PMC3168494

33.

Kim JS, Lê KA, Mahurkar S, Davis JN, Goran MI (2012) Influence of elevated liver fat on circulating adipocytokines and insulin resistance in obese Hispanic adolescents. Pediatr Obes 7(2):158–164. doi:10.1111/j.2047-6310.2011.00014.x Epub 2012 Feb 9. PubMed PMID: 22434756; PubMed Central PMCID: PMC3767148 CrossRefPubMedPubMedCentral

34.

Jarrar MH, Baranova A, Collantes R et al (2008) Adipokines and cytokines in non-alcoholic fatty liver disease. Aliment Pharmacol Ther 27(5):412–421 Epub 2007 Dec 10 PubMed PMID: 18081738 CrossRefPubMed

35.

Chu CJ, Lu RH, Wang SS et al (2007) Plasma levels of interleukin-6 and interleukin-8 in Chinese patients with non-alcoholic fatty liver disease. Hepatogastroenterology 54(79):2045–2048 PubMed PMID: 18251157 PubMed

36.

Huang YS, Chan CY, Wu JC, Pai CH, Chao Y, Lee SD (1996) Serum levels of interleukin-8 in alcoholic liver disease: relationship with disease stage, biochemical parameters and survival. J Hepatol 24:377–384CrossRefPubMed

37.

Bahcecioglu IH, Yalniz M, Ataseven H et al (2005) Levels of serum hyaluronic acid, TNF-alpha and IL-8 in patients with nonalcoholic steatohepatitis. Hepatogastroenterology 65:1549–1553

38.

Yamaguchi R, Yamamoto T, Sakamoto A et al (2015) Chemokine profiles of human visceral adipocytes from cryopreserved preadipocytes: neutrophil activation and induction of nuclear factor-kappa B repressing factor. Life Sci 143:225–230. doi:10.1016/j.lfs.2015.11.010 CrossRefPubMed

39.

Kobashi C, Asamizu S, Ishiki M et al (2009) Inhibitory effect of IL-8 on insulin action in human adipocytes via MAP kinase pathway. J Inflamm 6:25. doi:10.1186/1476-9255-6-25 CrossRef

40.

Marino F, Tozzi M, Schembri L et al (2015) Production of IL-8, VEGF and elastase by circulating and intraplaque neutrophils in patients with carotid atherosclerosis. PLoS ONE 10:e0124565. doi:10.1371/journal.pone.0124565 CrossRefPubMedPubMedCentral

41.

Kobashi C, Asamizu S, Ishiki M et al (2009) Inhibitory effect of IL-8 on insulin action in human adipocytes via MAP kinase pathway. J Inflamm (Lond) 6:25. doi:10.1186/1476-9255-6-25 PubMed PMID: 19709445; PubMed Central PMCID: PMC2746203 CrossRef

42.

Matsuda M, DeFronzo RA (1999) Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 22:1462–1470CrossRefPubMed

43.

Zozuliñska D, Majchrzak A, Sobieska M, Wiktorowicz K, Wierusz-Wysocka B (1999) Serum interleukin-8 level is increased in diabetic patients. Diabetologia 42:117–118CrossRefPubMed

44.

Esposito K, Nappo F, Giugliano F et al (2003) Cytokine milieu tends toward inflammation in type 2 diabetes. Diabetes Care 26:1647CrossRefPubMed

45.

Nomura S, Shouzu A, Omoto S, Nishikawa M, Fukuhara S (2000) Significance of chemokines and activated platelets in patients with diabetes. Clin Exp Immunol 121:437–443CrossRefPubMedPubMedCentral

46.

Samaras K, Botelho NK, Chisholm DJ, Lord RV (2010) Subcutaneous and visceral adipose tissue gene expression of serum adipokines that predict type 2 diabetes. Obesity (Silver Spring). 18(5):884–889. doi:10.1038/oby.2009.443 CrossRefPubMed

47.

Hajer GR, van Haeften TW, Visseren FL (2008) Adipose tissue dysfunction in obesity, diabetes, and vascular diseases. Eur Heart J 29(24):2959–2971. doi:10.1093/eurheartj/ehn387 CrossRefPubMed

48.

Carnethon MR, Rasmussen-Torvik LJ, Palaniappan L (2014) The obesity paradox in diabetes. Curr Cardiol Rep 16(2):446. doi:10.1007/s11886-013-0446-3 CrossRefPubMed

49.

Mancuso P (2016) The role of adipokines in chronic inflammation. Immunotargets Ther 5:47–56. doi:10.2147/ITT.S73223 CrossRefPubMedPubMedCentral

50.

Kwon H, Pessin JE (2013) Adipokines mediate inflammation and insulin resistance. Front Endocrinol 4:71. doi:10.3389/fendo.2013.00071 CrossRef

51.

Calton EK, Keane KN, Newsholme P, Soares MJ (2015) The impact of vitamin D levels on inflammatory status: a systematic review of immune cell studies. PLoS ONE 10:e0141770. doi:10.1371/journal.pone.0141770 CrossRefPubMedPubMedCentral

52.

Wei R, Christakos S (2015) Mechanisms underlying the regulation of innate and adaptive immunity by vitamin D. Nutrients 7:8251–8260. doi:10.3390/nu7105392 CrossRefPubMedPubMedCentral

53.

Jung CH, Kim KJ, Kim BY, Kim CH, Kang SK, Mok JO (2016) Relationship between vitamin D status and vascular complications in patients with type 2 diabetes mellitus. Nutr Res 2:117–124. doi:10.1016/j.nutres.2015.11.008 CrossRef

54.

Li DM, Zhang Y, Li Q, Xu XH, Ding B, Ma JH (2016) Low 25-hydroxy vitamin D level is associated with peripheral arterial disease in type 2 diabetes patients. Arch Med Res 47:49–54. doi:10.1016/j.arcmed.2016.01.007 CrossRefPubMed

55.

Hamdy Al-Said N, Abd El Ghaffar Mohamed N, Salam RF, Fawzy MW (2015) Vitamin D as a risk factor for premature atherosclerosis in patients with type 2 diabetes. Ther Adv Endocrinol Metab 6:249–257. doi:10.1177/2042018815600640 CrossRefPubMedPubMedCentral

56.

Chowdhury R, Kunutsor S, Vitezova A et al (2014) Vitamin D and risk of cause specific death: systematic review and meta-analysis of observational cohort and randomized intervention studies. BMJ 348:g1903. doi:10.1136/bmj.g1903 CrossRefPubMedPubMedCentral

Title: Circulating IL-8 levels are increased in patients with type 2 diabetes and associated with worse inflammatory and cardiometabolic profile
Authors: F. A. Cimini
I. Barchetta
A. Porzia
F. Mainiero
C. Costantino
L. Bertoccini
V. Ceccarelli
S. Morini
M. G. Baroni
A. Lenzi
M. G. Cavallo
Publication date: 01-10-2017
Publisher: Springer Milan
Published in: Acta Diabetologica / Issue 10/2017
Print ISSN: 0940-5429
Electronic ISSN: 1432-5233
DOI: https://doi.org/10.1007/s00592-017-1039-1

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Abstract

Aims

Methods

Results

Conclusions

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