Background Gout is considered an autoinflammatory disease characterized by activation of innate immunity. The presence of uric acid crystals causes oligomerization and dysfunctional activity of NPRL3 inflammasome macromolecules, resulting in hyperactivity of caspase-1. This process causes increased secretion of inflammatory cytokines such as IL-1β and IL-18. These cytokines, in turn, trigger a cascade of proinflammatory mediators, leading ultimately to endothelial activation and leukocyte recruitment. The main cytokines with secondary involvement in this process are IL-8 (neutrophil recruitment and activation), IL-6 (amplification of the inflammatory process, possible contribution to bone damage), TNFα (proinflammatory activation, maturation and increased monocyte to macrophage transformation). The association between serum cytokines levels and clinical manifestations of the disease, however, is not yet well understood.
Objectives Evaluated the serum profile of proinflammatory cytokines in gout (IL-1β, IL-6, IL-8, IL-17A, IL-18, IL-22 and IL-23) and described their relationship with clinical and laboratory data in a group of patients with the disorder
Methods This is a cross-sectional, observational study of 39 male patients with gout (GG), assessing the following variables: age, disease duration, body mass index (BMI), presence or not of comorbidities such as diabetes mellitus (DM), arterial hypertension (AH), dyslipidemia (DLD), and the presence of tophi, deformities and arthritis. Laboratory data on erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and uric acid were also analyzed. Levels of IL-1β, IL-6, IL-8, IL-17A, IL-18, IL-22 and IL-23 were measured by ELISA, following the supplier's recommendations. For the purposes of comparison, 34 males with no previous history of arthritis were also included in the study (CG).
Results The average age in the GG was 58.2 (±1.6) years and 54.3 (±1.8) years (p=0.102) in the CG. Seventeen participants (43%) exhibited active arthritis on evaluation. Levels of IL-18 were significantly higher in patients in relation to the CG (p=0.0013). No statistically significant differences were found between the GG and CG for the other measured cytokines. There was moderate correlation between IL-18 and ESR (R=0.43, p=0.0073), PCR (R=0.47, p=0.0025) and serum levels of IL-6 (R=0.36, p=0.023). No correlation was recorded between the cytokines analyzed and uric acid, age, time since diagnosis or the presence of comorbidities. An association was observed between serum levels of IL-6 and the presence of tophi (p=0.005) and deformities (p=0.0008), as well as a correlation between this cytokine and ESR (R=0.41, p=0.011) and CRP (R=0.48, p=0.02).
Conclusions IL-18 was correlated with inflammatory activity in gout, as well as IL-6 levels, while IL-6 was associated with clinical and laboratory activity, the presence of tophi and deformities, and may be a prognostic marker or influence the development of joint damage this pathology.
Disclosure of Interest None declared