• 1
    Yudkin, J. S., Stehouwer, C. D., Emeis, J. J., Coppack, SW (1999) C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue? Arterioscler Thromb Vasc Biol. 19: 972978.
  • 2
    Mishima, Y., Kuyama, A., Tada, A., Takahashi, K., Ishioka, T., Kibata, M. (2001) Relationship between serum tumor necrosis factor-alpha and insulin resistance in obese men with type 2 diabetes mellitus. Diabetes Res Clin Pract. 52: 119123.
  • 3
    Winkler, G., Kiss, S., Keszthelyi, L., et al (2003) Expression of tumor necrosis factor (TNF)-alpha protein in the subcutaneous and visceral adipose tissue in correlation with adipocyte cell volume, serum TNF-alpha, soluble serum TNF-receptor-2 concentrations and C- peptide level. Eur J Endocrinol. 149: 129135.
  • 4
    Hak, A. E., Stehouwer, C. D., Bots, M. L., et al (1999) Associations of C-reactive protein with measures of obesity, insulin resistance, and subclinical atherosclerosis in healthy, middle-aged women. Arterioscler Thromb Vasc Biol. 19: 19861991.
  • 5
    Carey, A. L., Bruce, C. R., Sacchetti, M., et al (2004) Interleukin-6 and tumor necrosis factor-alpha are not increased in patients with type 2 diabetes: evidence that plasma interleukin-6 is related to fat mass and not insulin responsiveness. Diabetologia 47: 10291037.
  • 6
    Retnakaran, R., Hanley, A. J., Raif, N., Connelly, P. W., Sermer, M., Zinman, B. (2003) C-reactive protein and gestational diabetes: the central role of maternal obesity. J Clin Endocrinol Metab. 88: 35073512.
  • 7
    Mohamed-Ali, V., Goodrick, S., Rawesh, A., et al (1997) Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-alpha, in vivo. J Clin Endocrinol Metab. 82: 41964200.
  • 8
    Hotamisligil, G. S., Arner, P., Caro, J. F., Atkinson, R. L., Spiegelman, BM (1995) Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest. 95: 24092415.
  • 9
    Petersen, A. M., Pedersen, BK (2005) The anti-inflammatory effect of exercise. J Appl Physiol. 98: 11541162.
  • 10
    Blankenberg, S., Tiret, L., Bickel, C., et al (2002) Interleukin-18 is a strong predictor of cardiovascular death in stable and unstable angina. Circulation 106: 2430.
  • 11
    Frigerio, S., Hollander, G. A., Zumsteg, U. (2002) Functional IL-18 is produced by primary pancreatic mouse islets and NIT-1 beta cells and participates in the progression towards destructive insulitis. Horm Res. 57: 94104.
  • 12
    Oikawa, Y., Shimada, A., Kasuga, A., et al (2003) Systemic administration of IL-18 promotes diabetes development in young non-obese diabetic mice. J Immunol. 171: 58655875.
  • 13
    Kretowski, A., Mironczuk, K., Karpinska, A., et al (2002) Interleukin-18 promoter polymorphisms in type 1 diabetes. Diabetes 51: 33473349.
  • 14
    Aso, Y., Okumura, K., Takebayashi, K., Wakabayashi, S., Inukai, T. (2003) Relationships of plasma interleukin-18 concentrations to hyperhomocysteinemia and carotid intimal-media wall thickness in patients with type 2 diabetes. Diabetes Care 26: 26222627.
  • 15
    Moriwaki, Y., Yamamoto, T., Shibutani, Y., et al (2003) Elevated levels of interleukin-18 and tumor necrosis factor-alpha in serum of patients with type 2 diabetes mellitus: relationship with diabetic nephropathy. Metabolism 52: 605608.
  • 16
    Esposito, K., Marfella, R., Giugliano, D. (2004) Plasma interleukin-18 concentrations are elevated in type 2 diabetes. Diabetes Care 27: 272.
  • 17
    Fischer, C. P., Perstrup, L. B., Berntsen, A., Eskildsen, P., Pedersen, BK (2005) Elevated plasma interleukin-18 is a marker of insulin-resistance in type 2 diabetic and non-diabetic humans. Clin Immunol. 117: 152160.
  • 18
    Esposito, K., Nappo, F., Marfella, R., et al (2002) Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress. Circulation 106: 20672072.
  • 19
    Escobar-Morreale, H. F., Botella-Carretero, J. I., Villuendas, G., Sancho, J., Millan, San JL (2004) Serum interleukin-18 concentrations are increased in the polycystic ovary syndrome: relationship to insulin resistance and to obesity. J Clin Endocrinol Metab. 89: 806811.
  • 20
    Lindegaard, B., Hansen, A. B., Pilegaard, H., Keller, P., Gerstoft, J., Pedersen, BK (2004) Adipose tissue expression of IL-18 and HIV-associated lipodystrophy. AIDS 18: 19561958.
  • 21
    Lindegaard, B., Hansen, A. B., Gerstoft, J., Pedersen, BK (2004) High plasma level of interleukin-18 in HIV-infected subjects with lipodystrophy. J AIDS 36: 588593.
  • 22
    Blair, S. N., Cheng, Y., Holder, JS (2001) Is physical activity or physical fitness more important in defining health benefits? Med Sci Sports Exerc. 33 (6 Suppl): S379S399.
  • 23
    Starkie, R., Ostrowski, S. R., Jauffred, S., Febbraio, M., Pedersen, BK (2003) Exercise and IL-6 infusion inhibit endotoxin-induced TNF-alpha production in humans. FASEB J. 17: 884886.
  • 24
    Keller, C., Keller, P., Giralt, M., Hidalgo, J., Pedersen, BK (2004) Exercise normalises overexpression of TNF-alpha in knockout mice. Biochem Biophys Res Commun. 321: 179182.
  • 25
    Narins, C. R., Zareba, W., Moss, A. J., et al (2004) Relationship between intermittent claudication, inflammation, thrombosis, and recurrent cardiac events among survivors of myocardial infarction. Arch Intern Med. 164: 440446.
  • 26
    Pilegaard, H., Ordway, G. A., Saltin, B., Neufer, PD (2000) Transcriptional regulation of gene expression in human skeletal muscle during recovery from exercise. Am J Physiol Endocrinol Metab. 279: E806E814.
  • 27
    Pilegaard, H., Saltin, B., Neufer, PD (2003) Exercise induces transient transcriptional activation of the PGC-1alpha gene in human skeletal muscle. J Physiol. 546: 851858.
  • 28
    Lundby, C., Nordsborg, N., Kusuhara, K., Kristensen, K. M., Neufer, P. D., Pilegaard, H. (2005) Gene expression in human skeletal muscle: alternative normalization method and effect of repeated biopsies. Eur J Applied Physiol. 95: 351360.
  • 29
    Matthews, D. R., Hosker, J. P., Rudenski, A. S., Naylor, B. A., Treacher, D. F., Turner, RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28: 412419.
  • 30
    Wallace, T. M., Levy, J. C., Matthews, DR (2004) Use and abuse of HOMA modeling. Diabetes Care 27: 14871495.
  • 31
    Esposito, K., Pontillo, A., Ciotola, M., et al (2002) Weight loss reduces interleukin-18 levels in obese women. J Clin Endocrinol Metab. 87: 38643866.
  • 32
    Esposito, K., Pontillo, A., di, P. C., et al (2003) Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. JAMA 289: 17991804.
  • 33
    Esposito, K., Nappo, F., Giugliano, F., et al (2003) Cytokine milieu tends toward inflammation in type 2 diabetes. Diabetes Care 26: 1647.
  • 34
    Skurk, T., Kolb, H., Muller-Scholze, S., Rohrig, K., Hauner, H., Herder, C. (2005) The proatherogenic cytokine interleukin-18 is secreted by human adipocytes. Eur J Endocrinol. 152: 863868.
  • 35
    Trayhurn, P., Beattie, JH (2001) Physiological role of adipose tissue: white adipose tissue as an endocrine and secretory organ. Proc Nutr Soc. 60: 329339.
  • 36
    Chung, H. Y., Sung, B., Jung, K. J., Zou, Y., Yu, BP (2006) The molecular inflammatory process in aging. Antioxid Redox Signal 8: 572581.
  • 37
    Bruun, J. M., Helge, J. W., Richelsen, B., Stallknecht, B. (2006) Diet and exercise reduce low-grade inflammation and macrophage infiltration in adipose tissue but not in skeletal muscle in severely obese subjects. Am J Physiol Endocrinol Metab. 290: E961E967.
  • 38
    Kohut, M. L., McCann, D. A., Russell, D. W., et al (2006) Aerobic exercise, but not flexibility/resistance exercise, reduces serum IL-18, CRP, and IL-6 independent of beta-blockers BMI, and psychosocial factors in older adults. Brain Behav Immun. 20: 201209.
  • 39
    Keller, C., Keller, P., Marshal, S., Pedersen, BK (2003) IL-6 gene expression in human adipose tissue in response to exercise—effect of carbohydrate ingestion. J Physiol. 550: 927931.
  • 40
    Frydelund-Larsen, L., Akerstrom, T., Nielsen, S., Keller, P., Keller, C., Pedersen, BK (2006) Visfatin mRNA expression in human subcutaneous adipose tissue is regulated by exercise. Am J Physiol Endocrinol Metab. 292: 2431.
  • 41
    Neumayr, G., Ludwiczek, O., Hoertnagl, H., et al (2005) The impact of prolonged strenuous endurance exercise on interleukin 18 and interleukin 18 binding protein in recreational cyclists. Int J Sports Med. 26: 836840.