Weight loss reduces interleukin-18 levels in obese women.

Obesity is associated with an increased risk of developing atherosclerosis, which may be mediated, at least in part, by increased secretion of proinflammatory cytokines by adipose tissue. We examined the hypothesis that circulating levels of IL-18 were elevated in obese women and would be reduced by weight loss. In a sample of 40 obese (body mass index, 36.4 +/- 3.1 kg/m(2)) women we found that plasma IL-18 levels were higher than in 40 normal weight control women (P < 0.01) and were positively associated with body weight (r = 0.46; P < 0.01) and visceral fat (waist to hip ratio; r = 0.39; P < 0.01). Caloric restriction-induced weight loss (> or = 10% of original weight) over 1 yr reduced IL-18 levels from 247 (204/309) to 147 (111/210) pg/ml (medians and 25%/75%; P < 0.01), positively associated with changes in body mass index and waist to hip ratio. In obese women, IL-18 levels are associated with body weight and abdominal fat deposition; weight loss is an important intervention to reduce IL-18 levels. IL-18 may be a novel cytokine operating in human obesity.

[1]  M. Pfeffer,et al.  Elevation of tumor necrosis factor-alpha and increased risk of recurrent coronary events after myocardial infarction. , 2000, Circulation.

[2]  S. Coppack,et al.  C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue? , 1999, Arteriosclerosis, thrombosis, and vascular biology.

[3]  P. Ridker.  On evolutionary biology, inflammation, infection, and the causes of atherosclerosis. , 2002, Circulation.

[4]  R. Tracy.  Is visceral adiposity the "enemy within"? , 2001, Arteriosclerosis, thrombosis, and vascular biology.

[5]  E. Bruckert,et al.  Elevated levels of interleukin 6 are reduced in serum and subcutaneous adipose tissue of obese women after weight loss. , 2000, The Journal of clinical endocrinology and metabolism.

[6]  G. Desideri,et al.  Early upregulation of endothelial adhesion molecules in obese hypertensive men. , 1999, Hypertension.

[7]  E. Bonora,et al.  Relation between soluble adhesion molecules and insulin sensitivity in type 2 diabetic individuals: role of adipose tissue. , 2001, Diabetes care.

[8]  R. Simsolo,et al.  The expression of tumor necrosis factor in human adipose tissue. Regulation by obesity, weight loss, and relationship to lipoprotein lipase. , 1995, The Journal of clinical investigation.

[9]  P. Vallance,et al.  Inflammatory cytokines impair endothelium-dependent dilatation in human veins in vivo. , 1997, Circulation.

[10]  L. Heilbronn,et al.  Energy Restriction and Weight Loss on Very-Low-Fat Diets Reduce C-Reactive Protein Concentrations in Obese, Healthy Women , 2001, Arteriosclerosis, thrombosis, and vascular biology.

[11]  H. Okamura,et al.  Interleukin-18: a novel cytokine that augments both innate and acquired immunity. , 1998, Advances in immunology.

[12]  P. Libby,et al.  Inflammation and Atherosclerosis , 2002, Circulation.

[13]  James L. Young,et al.  Expression of Interleukin (IL)-18 and Functional IL-18 Receptor on Human Vascular Endothelial Cells, Smooth Muscle Cells, and Macrophages , 2002, The Journal of experimental medicine.

[14]  K. Flegal,et al.  Increasing Prevalence of Overweight Among US Adults: The National Health and Nutrition Examination Surveys, 1960 to 1991 , 1994 .

[15]  J S Yudkin,et al.  Journal of Clinical Endocrinology and Metabolism Printed in U.S.A. Copyright © 1997 by The Endocrine Society Subcutaneous Adipose Tissue Releases Interleukin-6, But Not Tumor Necrosis Factor-�, in Vivo* , 2022 .

[16]  G. Gamble,et al.  The influences of obesity and glycemic control on endothelial activation in patients with type 2 diabetes. , 2001, The Journal of clinical endocrinology and metabolism.

[17]  G. Ciliberto,et al.  Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment. , 1997, Immunity.

[18]  R. Marfella,et al.  Reduction of Inflammatory Cytokine Concentrations and Improvement of Endothelial Functions in Obese Women After Weight Loss Over One Year , 2002, Circulation.

[19]  H. Cohen,et al.  Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly. , 1999, The American journal of medicine.

[20]  J. Stephens,et al.  Regulation of transcription factor mRNA accumulation during 3T3-L1 preadipocyte differentiation by tumour necrosis factor-alpha. , 1992, Journal of molecular endocrinology.

[21]  E. Poehlman,et al.  Weight Loss Reduces C-Reactive Protein Levels in Obese Postmenopausal Women , 2002, Circulation.

[22]  A. Siegbahn,et al.  Relationship between interleukin 6 and mortality in patients with unstable coronary artery disease: effects of an early invasive or noninvasive strategy. , 2001, JAMA.

[23]  A. Tedgui,et al.  Expression of Interleukin-18 in Human Atherosclerotic Plaques and Relation to Plaque Instability , 2001, Circulation.