Journal of Endocrinological Investigation

, Volume 38, Issue 3, pp 339–343 | Cite as

Interleukin-6, soluble interleukin-6 receptor/interleukin-6 complex and insulin resistance in obese children and adolescents

  • G. De FilippoEmail author
  • D. Rendina
  • F. Moccia
  • V. Rocco
  • A. Campanozzi
Original Article



To study the characteristics of interleukin 6 (IL6), soluble form of interleukin 6 receptor (sILR)/IL6 complex in obese children and adolescents and its relationship with insulin resistance (IR).

Subjects and methods

66 obese children and adolescents [34 boys, mean age 10.3 ± 2.9 years, z-score of body mass index (BMI) 4.76 ± 1.36] and 24 non-obese healthy sex- and age-matched controls. Fasting levels of glucose, insulin, IL6, sIL6, sgp130 were measured. IR was assessed by homeostasis model assessment of IR (HOMA-IR).


Obese subjects showed increased levels of insulin and IL-6 and higher HOMA-IR compared to controls (117.67 ± 50.9 vs. 62.42 ± 29.4 pmol/L, 2.73 ± 0.98 vs. 1.07 ± 0.41 pg/ml and 4.03 ± 2.16 vs. 1.83 ± 1.05 for insulin, IL-6 and HOMA-IR, respectively, p < 0.01 in all cases). sIL-6R levels were significantly lower in obese subjects (34.7 ± 14.2 vs. 55.6 ± 15.2 ng/ml in controls, p = 0.005), whereas sgp130 levels were not significantly different. In obese subjects, IL-6 directly correlated with z-score BMI (r = 0.481, p = 0.009) and with waist-to-height ratio (r = 0.494, p = 0.007), while sIL6-R was inversely related to HOMA-IR (r = −0.522, p = 0.002). Insulin resistant subjects showed higher levels of IL6 and lower levels of sIL6R (3.31 ± 0.72 vs. 2.25 ± 0.64 pg/ml, p = 0.020 and 25.3 ± 9.3 vs. 42.5 ± 10.4 ng/ml, p = 0.013, respectively).


In obese children and adolescents, IR is associated with elevated levels of IL-6 and diminished values of sIL-6R.


Obesity Insulin resistance IL-6 Transsignalling Pediatrics 



Body mass index


Homeostasis model of assessment-insulin resistance


Insulin resistance


Interleukin 6


Interleukin 6 receptor


Soluble form of interleukin 6 receptor



This study was supported by a grant of University of Foggia (Italy).

Conflict of interest

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.


  1. 1.
    Weiss R, Dziura J, Burgert TS et al (2004) Obesity and the metabolic syndrome in children and adolescents. N Engl J Med 350:2362–2374CrossRefPubMedGoogle Scholar
  2. 2.
    Viggiano D, De Filippo G, Rendina D et al (2009) Screening of metabolic syndrome in obese children: a primary care concern. J Pediatr Gastroenterol Nutr 49:329–334CrossRefPubMedGoogle Scholar
  3. 3.
    Senn JJ, Klover PJ, Nowak IA, Mooney RA (2002) Interleukin-6 induces cellular insulin resistance in hepatocytes. Diabetes 51:3391–3399CrossRefPubMedGoogle Scholar
  4. 4.
    Galcheva SV, Iotova VM, Yotov YT, Bernasconi S, Street ME (2011) Circulating proinflammatory peptides related to abdominal adiposity and cardiometabolic risk factors in healthy prepubertal children. Eur J Endocrinol 164:553–558CrossRefPubMedGoogle Scholar
  5. 5.
    Scheller J, Rose-John S (1997) Interleukin-6 family of cytokines. Annu Rev Immunol 15:797–819CrossRefGoogle Scholar
  6. 6.
    Kallen KJ (2002) The role of transsignalling via the agonistic soluble IL-6 receptor in human diseases. Biochim Biophys Acta 1592:323–343CrossRefPubMedGoogle Scholar
  7. 7.
    Schuett H, Luchtefeld M, Grothusen C et al (2009) How much is too much? Interleukin 6 and its signalling in atherosclerosis. Thromb Haemost 102:215–222PubMedGoogle Scholar
  8. 8.
    Weiss TW, Arnesen H, Selijefot I (2013) Components of the Interleukin-6 transsignalling system are associated with the metabolic syndrome, endothelial disfunction and arterial stiffness. Metab Clin Exp 62:1008–1013CrossRefPubMedGoogle Scholar
  9. 9.
    Cole TJ, Lobstein T (2012) Extended international (IOTF) body mass index cut-offs for thinness, overweight and obesity. Pediatr Obes 7:284–294CrossRefPubMedGoogle Scholar
  10. 10.
    Cole TJ (2002) A chart to link centiles of body mass index, weight and height. Eur J Clin Nutr 56:1194–1199CrossRefPubMedGoogle Scholar
  11. 11.
    Mattews DR, Hosker JP, Rudeski AS et al (1985) Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419CrossRefGoogle Scholar
  12. 12.
    D’Annunzio G, Vanelli M, Pistorio A et al (2009) Insulin resistance and secretion indexes in healthy Italian children and adolescents: a multicentre study. Acta Biomed 80:21–28PubMedGoogle Scholar
  13. 13.
    Fernández-Real JM, Ricart W (2003) Insulin resistance and chronic cardiovascular inflammatory syndrome. Endocr Rev 24:278–301CrossRefPubMedGoogle Scholar
  14. 14.
    Bastard JP, Maachi M, Lagathu C et al (2006) Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur Cytokine Netw 17:4–12PubMedGoogle Scholar
  15. 15.
    Vozarova B, Weyer C, Hanson K, Tataranni PA, Bogardus C, Pratley RE (2001) Circulating interleukin-6 in relation to adiposity, insulin action, and insulin secretion. Obes Res 94:14–417Google Scholar
  16. 16.
    Stith RD (1994) Luo J Endocrine and carbohydrate responses to interleukin-6 in vivo. Circ Shock 44:210–215PubMedGoogle Scholar
  17. 17.
    Petersen EW, Carey AL, Sacchetti M et al (2005) Acute IL-6 treatment increases fatty acid turnover in elderly humans in vivo and in tissue culture in vitro. Am J Physiol Endocrinol Metab 288:E155–E162CrossRefPubMedGoogle Scholar
  18. 18.
    Bastard JP, Maachi M, Tran Van Nhieu J et al (2002) Adipose tissue IL-6 content correlates with resistance to insulin activation of glucose uptake both in vivo and in vitro. J Clin Endocrinol Metab 87:2084–2089CrossRefPubMedGoogle Scholar
  19. 19.
    Mooney RA, Senn J, Cameron S et al (2001) Suppressors of cytokine signaling-1 and -6 associate with and inhibit the insulin receptor. A potential mechanism for cytokine-mediated insulin resistance. J Biol Chem 276:25889–25893CrossRefPubMedGoogle Scholar
  20. 20.
    Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419CrossRefPubMedGoogle Scholar
  21. 21.
    Reinehr T, Andler W (2004) Changes in the atherogenic risk factor profile according to degree of weight loss. Arch Dis Child 89:419–422CrossRefPubMedCentralPubMedGoogle Scholar
  22. 22.
    Keskin M, Kurtoglu S, Kendirci M, Atabek ME, Yazici C (2005) Homeostasis model assessment is more reliable than the fasting glucose/insulin ratio and quantitative insulin sensitivity check index for assessing insulin resistance among obese children and adolescents. Pediatrics 115:e500–e503CrossRefPubMedGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 2014

Authors and Affiliations

  • G. De Filippo
    • 1
    • 2
    • 6
    Email author
  • D. Rendina
    • 3
  • F. Moccia
    • 4
  • V. Rocco
    • 4
  • A. Campanozzi
    • 5
  1. 1.Pediatric Endocrinology UnitGaetano Rummo HospitalBeneventoItaly
  2. 2.Assistance Publique-Hôpitaux de Paris, Service d’Endocrinologie et Diabétologie PédiatriqueHôpitaux Universitaires Paris SudLe Kremlin-BicêtreFrance
  3. 3.Department of Clinical Medicine and SurgeryFederico II University of NaplesNaplesItaly
  4. 4.Biochemistry Unit, Gaetano Rummo HospitalBeneventoItaly
  5. 5.Pediatrics, Department of Medical and Surgical SciencesUniversity of FoggiaFoggiaItaly
  6. 6.Service d’Endocrinologie et Diabétologie PédiatriqueCentre Hospitalier Universitaire de BicêtreLe Kremlin-BicêtreFrance

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