Endocrine Abstracts

Introduction: Interleukin 18 (IL-18) is a proinflammatory and proatherogenic cytokine which is associated with obesity, insulin resistance and cardiovascular disease. It is supposed that insulin has anti-inflammatory action. The aim of the present study was to estimate serum IL-18 concentration in young healthy population, its regulation by hyperinsulinemia and relationship with insulin sensitivity and glucose and lipid oxidation.

Methods: We studied 36 healthy male subjects (mean age, 24.50±2.67; mean BMI, 25.77±3.70 kg/m²). Serum IL-18 concentration was measured before and after 2 hour euglycemic hyperinsulinemic clamp. In 18 subjects, clamp was prolonged to 6 hours and at the end an additional measurement of serum IL-18 was taken. Respiratory quotient (RQ) and glucose and lipid oxidation (LOx) were assessed with indirect calorimetry in the baseline state and every 2 hours of the clamp.

Results: Hyperinsulinemia decreased serum IL-18, this effect was present both in 2 and 6 hours of the clamp (both p<0.001). Additionally, serum IL-18 decreased from 2 to 6 hour (p=0.044). Two-hour and 6 hour serum IL-18 values were positively related to plasma free fatty acids in the respective time-points (r=0.43, P=0.033 and r=0.52, P=0.028). Two-hour and 6 hour serum IL-18 were also negatively related to RQ (r=−0.40, p=0.018 and r=−0.54, p=0.02) and positively to LOx (r=0.46, p=0.006 and r=0.66, p=0.004) in the respective time-points. Six-hour IL-18 was negatively related to insulin sensitivity calculated for the 6th hour of the clamp (r=−0.53, p=0.025). The change in serum IL-18 in response to insulin was inversely related to the white blood cell count (r=−0.52, P=0.027) and the neutrophil cell count (r=−0.56, P=0.016), i.e., the higher the cell count, the lower the decrease in IL-18.

Conclusion: Serum IL-18 is negatively regulated by hyperinsulinemia, suggesting anti-inflammatory effect of insulin. IL-18 is related to decreased insulin sensitivity mainly through its association with lipid oxidation.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details unavailable.