Dyslipidaemia and Cytokine Profile in Patients with Gout: The Role of IL-6, IL-18 and Hyperuricemia in the Development of Metabolic Disorders

Evaluation of the correlation of immunological and biochemical values with clinical manifestations of gout, as well as the role of hyperuricemia in comorbid states is an important for the search of therapeutic targets.

Objective: Investigation of the relationship between features of dyslipidaemia and immunological changes in patients with tophaceous gout and asymptomatic hyperuricemia.

Patients and Methods: The study has included 85 male patients: 1st (main) group – 49 patients with primary chronic gout according to criteria of Wallace S.L., 2nd (control) group – 36 patients with asymptomatic hyperuricemia. The levels of uric acid (UA), C-reactive protein (CRP), fasting glycaemia, lipid profile – total cholesterol (TC), triglycerides (TG), high-density (HDL), low density (LDL), very low density (VLDL) lipoproteins, atherogenic ratio (AR); concentrations of cytokine: interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), IL-4, IL-6, IL-8, IL-10 and IL-18 in the blood serum by enzyme-linked immunosorbent analysis.

Results: Values of UA have positively correlated with the number of affected joints (r=0.64, p=0.058), presence of tophi (r=0.73, p=0.042), glycaemic level (r=0.74; p=0.038). An increase of TC to 11.85%, LDL to 22.51%, VLDL to 21.43% and a decrease of HDL to 20.9% in patients with gout was observed. AR was higher in the group of patients with gout to 25.8% (p=0.0088). An increase of the production of cytokines IL-6 (p=0.0012) and IL-18 (p=0.0008) was observed in patients with gout whose level of UA was above 0.420 mmol/l. There was no significant increase of IL-1β (+0.36, p=0.0154), TNF-α (+0.21, p=0.0944), IL-4 (+0.02, p=0.0028). There was no relationship between IL-6 and CRP (r=0.26, p=0.0122). Strong correlation was shown in the 1st group between IL-6 and AR (r=0.762, p=0.0018), IL-18 and AR (r=0.766; p=0.0052). Correlation between IL-6 and AR was weaker (r=0.292, p=0.0127), as well as a weak negative correlation was observed in the 2nd group between IL-18 and AR (r=-0.366, p=0.0049).

Conclusion: The exceptional role of hyperuricemia in the development of dyslipidaemia in patients with gout has not been confirmed. TC, LDL, VLDL and AR are significantly elevated, while HDL is significantly lower in patients during the intercritical period of gout. The increase of IL-6 and IL-18 is accompanied by more prominent features of dyslipidaemia and clinical manifestations of gouty arthritis.