Elevated levels of interleukin-18 are associated with several indices of general and visceral adiposity and insulin resistance in women with polycystic ovary syndrome

Abstract

Objective: Our aim was to analyze levels of proinflammatory biomarker interleukin-18 (IL-18) in healthy controls and patients with polycystic ovary syndrome (PCOS) focusing on its association with obesity, clinical, hormonal, and metabolic characteristics. Subjects and methods: Fifty-eight patients with PCOS were enrolled in the study fulfilling the Rotterdam criteria and were matched for age, body mass index (BMI), and ethnicity with 30 healthy controls. Detailed anthropometric measurements, clinical investigations, hormonal and biochemical tests were obtained between the 3 rd and 5 th day of a menstrual cycle. A subanalysis of the PCOS group was performed separating patients into several groups according to a waist-to-height ratio (WHtR), insulin resistance (IR), and free androgen index (FAI). Serum IL-18 levels were measured using the ELISA method. Results: Levels of IL-18 were similar between PCOS patients and controls. IL-18 was higher in overweight/obese women compared to normal-weight women when analyzing all participants together and separately PCOS or controls group (p < 0.001, p < 0.001, p = 0.01, respectively). Additionally, IL-18 levels were higher in high-WHtR and IR subgroups compared to low-WHtR (p < 0.001) and non-IR PCOS women (p < 0.001). PCOS women with high FAI had greater serum IL-18 levels than normal-FAI patients (p = 0.002). Levels of IL-18 correlated positively with most of the anthropometric and metabolic parameters. In multiple linear regression, age, waist circumference, and fasting insulin were independently related factors with IL-18. Conclusion: Elevated levels of IL-18 were related to several indices of general and visceral adiposity and insulin resistance in PCOS.

Interleukin-18 cytokine in immunity, inflammation, and autoimmunity: Biological role in induction, regulation, and treatment

“…ovarian syndromea condition strongly linked to T1D (158,159). Taken together, the results of these numerous animal and human studies suggest that IL-18 may play a pathogenic role in T1D through its interferon gamma (IFN-g)-inducing potential.…”

“…Similar findings were observed after treatment with HIV-1 protease inhibitors in rats ( 157 ). IL-18 has also been shown to be a mediator of polycystic ovarian syndrome – a condition strongly linked to T1D ( 158 , 159 ). Taken together, the results of these numerous animal and human studies suggest that IL-18 may play a pathogenic role in T1D through its interferon gamma (IFN- γ)-inducing potential.…”

Serum uric acid/creatinine ratio and free androgen index are synergistically associated with increased risk of polycystic ovary syndrome in obese women

“…Serum uric acid is closely related to androgen excess which is the clue criterion of PCOS [ 19 ]: hyperandrogenemia increases serum uric acid by inducing hepatic metabolism of purine nucleotides and enhancing purine renewal in the kidney [ 47 , 48 ]. Indeed, hyperandrogenemia is associated with visceral obesity, insulin resistance and low inflammatory state [ 49 – 51 ]. Accumulation of visceral adipose tissue stimulates uric acid synthesis through de novo purine synthesis in the pentose phosphate pathway [ 52 ] in turn, uric acid induces intracellular and mitochondrial oxidative stress leading to increased fat synthesis and impaired fatty acid oxidation through disturbances in the Krebs cycle [ 53 , 54 ].…”

Mechanisms and Target Parameters in Relation to Polycystic Ovary Syndrome and Physical Exercise: Focus on the Master Triad of Hormonal Changes, Oxidative Stress, and Inflammation

“…Furthermore, IL-18 values showed a positive correlation with obesity, IR, and hyperandrogenism [ 96 ]. By contrast, Kabakchieva et al demonstrated no significant difference in IL-18 levels between healthy women and those with PCOS [ 97 ]. Numerous studies found a relationship between IL-18 levels and obesity, but not between IL-18 and PCOS specifically [ 98 , 99 ].…”