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Serum Interleukin-18 Concentrations Are Increased in the Polycystic Ovary Syndrome: Relationship to Insulin Resistance and to Obesity

Departments of Endocrinology (H.F.E.-M., J.I.B.-C., G.V., J.S.) and Molecular Genetics (J.L.S.M.), Hospital Ramón y Cajal, E-28034 Madrid, Spain

Address all correspondence and requests for reprints to: Héctor F. Escobar-Morreale, M.D., Ph.D., Department of Endocrinology, Hospital Ramón y Cajal, Carretera de Colmenar Km 9100, E-28034 Madrid, Spain. E-mail: hescobarm.hrc{at}salud.madrid.org.

Low-grade chronic inflammation is involved in the pathogenesis of the metabolic syndrome and atherosclerosis, and serum levels of inflammatory cytokines are useful cardiovascular risk markers. We have studied serum IL-18 concentrations in women with polycystic ovary syndrome (PCOS), focusing on its relationship with obesity and indexes of insulin resistance.

Sixty consecutive women with PCOS and 34 healthy women were recruited. Serum levels of IL-18 and lipid and hormone profiles were measured. The insulin sensitivity index was calculated from glucose and insulin concentrations during an oral glucose tolerance test. Data were submitted to a multivariate general linear model introducing age as a covariate.

Serum IL-18 levels were increased in PCOS patients compared with controls (P = 0.031) and in obese women compared with lean women (P = 0.018). No interaction between PCOS and obesity was found, suggesting that the influence of PCOS on serum IL-18 concentrations studied here was not different in lean women compared with obese women and that the influence of obesity on serum IL-18 concentrations was the same in the PCOS and control groups. Serum IL-18 levels correlated, after logarithmic transformation, with body mass index (r = 0.38; P < 0.0002), waist-to-hip ratio (r = 0.33; P < 0.001), and total testosterone levels (r = 0.24; P < 0.02), and inversely with the insulin sensitivity index (r = -0.23; P < 0.03).

In conclusion, PCOS and obesity induce an increase in serum IL-18 levels, which are also associated with several indexes of global and visceral adiposity and with insulin resistance.

This work was supported by Grants FIS 02/0741 and RGDM G03/212 from the Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo, and by Grant CAM 08.6/0010/2001, Consejería de Educación, Comunidad de Madrid, Spain.

Abbreviations: BMI, Body mass index; CRP, C-reactive protein; DHEAS, dehydroepiandrosterone-sulfate; GLM, general linear model; HDL, high-density lipoprotein; ISI, insulin sensitivity index; LDL, low-density lipoprotein; PCOS, polycystic ovary syndrome; WHR, waist-to-hip ratio.

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