Download PDF
Horm Metab Res 2006; 38(8): 507-512
DOI: 10.1055/s-2006-949122
Original Clinical

© Georg Thieme Verlag KG Stuttgart · New York

IL-18: Relationship with Anthropometry, Body Composition Parameters, Leptin and Arterial Hypertension

N. Vilarrasa 1 , J. Vendrell 2 , J. Maravall 1 , M. Broch 2 , A. Estepa 1 , A. Megia 2 , J. Soler 1 , I. Simón 2 , C. Richart 2 , J. M. Gómez 1
  • 1Endocrinology and Diabetes Unit, Hospital Universitari de Bellvitge, Barcelona, Spain
  • 2Endocrinology and Research Unit, Hospital Universitari de Tarragona Joan XXIII, Rovira I Virgili University, Tarragona, Spain
Further Information

Publication History

Received 18 July 2005

Accepted after revision 17 January 2006

Publication Date:
29 August 2006 (online)

Also available at
    Permissions and Reprints

Abstract

Objective: Interleukin-18 (IL-18) is a potent pro-inflammatory cytokine with potential atherogenic properties whose role in human obesity has been recently suggested. The aim of our study was to analyze the physiologic distribution of IL-18 among sexes and all decades of the adult life in a healthy population randomly selected and to study its relationship with anthropometric, body composition measurements and leptin concentrations. We also studied the relationship of IL-18 with smoking and arterial hypertension, known risk factors implicated in atherogenesis. Materials and Methods: One hundred and thirty four men and 127 healthy women were included in the study. Plasma concentrations of IL-18 and leptin were determined in all subjects. Body composition was evaluated by bioelectrical impedanciometry. Results: IL-18 was distributed similarly in men and women and throughout decades. No significant differences were found in IL-18 between obese and normal-weight men and women according to their body mass index and body fat content. Higher IL-18 concentrations were found in subjects with arterial hypertension. In the bivariate correlation analysis only waist to hip ratio correlated weakly with IL-18 in the whole population (r=0.12, p=0.04). In the multiple regression analysis the relationship between IL-18 and waist to hip ratio lost significance after adjusting for age, sex and body mass index. However, IL-18 remained associated with arterial hypertension (adjusted r2=0.25, p=0.023). Conclusions: The lack of correlation between IL-18 with anthropometric, body composition variables and leptin in our healthy population argues against a role of this cytokine in obesity. Moreover, our findings suggest the implication of this interleukin in the atherogenic process induced by arterial hypertension.

Key words

Inflammation - cytokine - interleukin - obesity - body fat

References

  • 1 Kopelman PG. Obesity as a medical problem.  Nature. 2000;  404 635-643
    CrossrefPubMedGoogle Scholar
  • 2 Yudkin JS, Stehouwer CD, Emeis JJ, Coppack SW. C-reactive protein in healthy subjects: associations with obesity, insulin resistance, endothelial dysfunction: a potential role for cytokines originating from adipose tissue?.  Arterioscler Thromb Vasc Biol. 1999;  19 972-978
    CrossrefPubMedGoogle Scholar
  • 3 Trayhurn P, Beattie JH. Physiological role of adipose tissue: white adipose tissue as an endocrine and secretory organ.  Proc Nutr Soc. 2001;  60 329-339
    CrossrefPubMedGoogle Scholar
  • 4 Kern PA, Saghizadeh M, Ong JM, Bosch RJ, Deem R, Simsolo RB. The expression of tumor necrosis factor in human adipose tissue. Regulation by obesity, weight loss, and relationship to lipoprotein lipase.  J Clin Invest. 1995;  95 2111-2119
    CrossrefPubMedGoogle Scholar
  • 5 Mohamed-Ali V, Goodrick S, Rawesh A, Katz DR, Miles JM, Yudkin JS, Klein S, Coppack SW. Subcutaneous adipose tissue releases interleukin-6 but not tumor necrosis factor-alpha, in vivo.  J Clin Endocrinol Metab. 1997;  82 4196-4200
    CrossrefPubMedGoogle Scholar
  • 6 Stephens JM, Butts MD, Pekala PH. Regulation of transcription factor mRNA accumulation during 3T3-L1 preadipocyte differentiation by tumor necrosis factor-alpha.  J Mol Endocrinol. 1992;  9 61-72
    PubMedGoogle Scholar
  • 7 Okamura H, Tsutsui H, Kashiwamura S, Yoshimoto T, Nakanishi K. Interleukin-18: a novel cytokine that augments both innate and acquired immunity.  Adv Immunol. 1998;  70 281-312
    PubMedGoogle Scholar
  • 8 Dinarello CA. Interleukin-18, a proinflammatory cytokine.  Eur Cytokine Netw. 2000;  11 483-486
    PubMedGoogle Scholar
  • 9 Mc Innes IB, Gracie JA, Leung BP, Wei XQ, Liew FY. Interleukin 18: a pleiotropic participant in chronic inflammation.  Immunol Today. 2000;  21 312-315
    CrossrefPubMedGoogle Scholar
  • 10 Gerdes N, Sukhova GK, Libby P, Reynolds RS, Young JL, Schönbeck U. Expression of interleukin (IL)-18 and functional IL-18 receptor on human vascular endothelial cells, smooth muscle cells and macrophages: implications for atherogenesis.  J Exp Med. 2002;  195 245-257
    CrossrefPubMedGoogle Scholar
  • 11 Mallat Z, Henry P, Fressonnet R, Alouani S, Scoazec A, Beaufils P, Chvatchko Y, Tedgui A. Increased plasma concentrations of interleukin-18 in acute coronary syndromes.  Heart. 2002;  88 467-469
    CrossrefPubMedGoogle Scholar
  • 12 Seta Y, Kanda T, Tanaka T, Arai M, Sekiguchi K, Yokoyama T, Kurimoto M, Tamura J, Kurubayashi M. Interleukin 18 in acute myocardial infarction (Lett).  Heart. 2000;  84 688
    PubMedGoogle Scholar
  • 13 Mallat Z, Corbaz A, Scoazec A, Besnard S, Leseche G, Chvatchko Y, Tedgui A. Expression of Interleukin-18 in human atherosclerotic plaques and relation to plaque instability.  Circulation. 2001;  104 1598-1603
    PubMedGoogle Scholar
  • 14 Mallat Z, Corbaz A, Scoazec A, Graber P, Alouani S, Esposito B, Humbert Y, Chvatchko Y, Tedgui A. Interleukin-18/interleukin-18 binding protein signaling modulates atherosclerotic lesion development and stability.  Circ Res. 2001;  89 E41-E45
    PubMedGoogle Scholar
  • 15 Blankenberg S, Tiret L, Bickel C, Peetz D, Cambien F, Meyer J, Rupprecht H. Interleukin-18 is a strong predictor of cardiovascular death in stable and unstable angina.  Circulation. 2002;  106 24-30
    CrossrefPubMedGoogle Scholar
  • 16 Esposito K, Pontillo A, Ciotola M, Di Palo C, Grella E, Nicoletti G, Giugliano D. Weight loss reduces interleukin-18 levels in obese women.  J Clin Endocrinol Metab. 2002;  87 3864-3866
    CrossrefPubMedGoogle Scholar
  • 17 Esposito K, Pontillo A, Di Palo C, Giugliano G, Masella M, Marfella R, Giugliano D. Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial.  JAMA. 2003;  289 1799-1804
    CrossrefPubMedGoogle Scholar
  • 18 Escobar-Morreale, Botella-Carretero J, Villuendas G, Sancho J, San Millan JL. Serum interleukin-18 concentrations are increased in the polycystic ovary syndrome: relationship to insulin resistance and to obesity.  J Clin Endocrinol Metab. 2004;  89 806-811
    CrossrefPubMedGoogle Scholar
  • 19 Olusi SO, Al-Awadhi A, Abraham M. Relations of serum interleukin 18 levels to serum lipid and glucose concentrations in an apparently healthy adult population.  Horm Res. 2003;  60 29-33
    CrossrefPubMedGoogle Scholar
  • 20 Gardner G, Halweil B. Hunger, escaping excess.  World Watch. 2000;  13 25-35
    PubMedGoogle Scholar
  • 21 Kyle UG, Bosaeus I, De Lorenzo AD, Deurenberg P, Elia M, Manuel Gómez J, Lilienthal Heitmann B, Kent-Smith L, Melchior JC, Pirlich M, Scharfetter H, MWJ Schols A, Pichard C. ESPEN. Bioelectrical impedance analysis - Part II: utilization in clinical practice.  Clin Nutr. 2004;  23 1430-1453
    CrossrefPubMedGoogle Scholar
  • 22 Ferrucci L, Corsi A, Lauretani F, Bandinelli S, Bartali B, Taub DD, Guralnik JM, Longo DL. The origins of age-related proinflammatory state.  Blood. 2005;  105 2294-2299
    CrossrefPubMedGoogle Scholar
  • 23 Hung J, McQuillan BM, Chapman CM, Thompson PL, Beilby JP. Elevated interleukin-18 levels are associated with the metabolic syndrome independent of obesity and insulin resistance.  Arterioscler Thromb Vasc Biol. 2005;  25 1268-1273
    CrossrefPubMedGoogle Scholar
  • 24 Blankenberg S, Luc G, Ducimetière P, Arveiler D, Ferrières J, Amouyel P, Evans A, Cambien F, Tiret L. PRIME Study Group . Interleukin-18 and the risk of coronary heart disease in European men. The Prospective Epidemiological Study of Myocardial Infarction (PRIME).  Circulation. 2003;  108 2453-2459
    CrossrefPubMedGoogle Scholar
  • 25 Aso Y, Okumura K, Takebayashi K, Wakabayashi S, Inukai T. Relationships of plasma interleukin-18 concentrations to hyperhomocysteinemia and carotid intimal-media wall thickness in patients with type 2 diabetes.  Diabetes Care. 2003;  26 2622-2627
    PubMedGoogle Scholar
  • 26 Bosch M, López-Bermejo A, Vendrell J, Musri M, Ricart W, Fernández-Real JM. Circulating IL-18 concentration is associated with insulin sensitivity and glucose tolerance through increased fat-free mass.  Diabetologia. 2005;  48 1841-1843
    CrossrefPubMedGoogle Scholar
  • 27 Skurk T, Kolb H, Müller-Scholze S, Röhrig K, Hauner H, Herder C. The proatherogenic cytokine interleukin-18 is secreted by human adipocytes.  Eur J Endocrinol. 2005;  152 863-868
    CrossrefPubMedGoogle Scholar
  • 28 Marfella R, Siniscalchi M, Nappo F, Gualdiero P, Esposito K, Sasso FC, Cacciapuoti F, Di Filippo C, Rossi F, D'Amico M, Giugliano D. Regression of carotid atherosclerosis by control of morning blood pressure peak in newly diagnosed hypertensive patients.  Am J Hypertens. 2005;  18 308-318
    CrossrefPubMedGoogle Scholar

Correspondence

Nuria VilarrasaGarcía 

C/Rambla Just Oliveras·N° 64, 3° 2a escalera A·08901 L'Hospitalet de Llobregat· Barcelona·Spain

Phone: +34/93/533 85 11

Fax: +34/93/337 52 48

Email: nuriavilarrasa@yahoo.es