Background: Rheumatic heart disease (RHD) remains a serious public health problem in developing countries. The pattern of immune response after exposure to streptococcus is one of the main determinants of the rheumatic inflammatory process, making it essential to identify the patients who present a higher risk of disease progression. The objective was to analyze cytokine serum levels in the different stages of RHD, and their correlation with disease severity, stratified by the need for valve intervention.
Methods: Eight-nine patients with rheumatic mitral valve (MV) disease were selected. Echocardiogram was performed in all patients to quantify valve disease severity and hemodynamic measurements. Serum samples were analyzed using cytometric bead array assay for the measurement of interleukins (IL): IL-10, IL-6, IL-2, IL-4, IL-17A, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ).
Results: Mean age was 41 ± 11.5 years, 85% women. MV was affected in all cases, with 60 patients (67.4%) presenting isolated mitral involvement. At the time of inclusion, 64 patients had already undergone some valvular intervention, either percutaneous or surgical procedures. Patients with mild or moderate MV disease reported earlier onset of secondary prophylaxis compared to patients with severe RHD (15.7 ± 10.5 versus 23.9 ± 10.2 years, p = 0.002). The peripheral serum concentration of inflammatory cytokines (IL-6, TNF-α, IL-2, IL-4, IL-17A, IFN-γ) was higher in the group with more severe disease. The expression of the anti-inflammatory cytokine IL-10 was similar between the groups (p = 0.366). Cluster analysis of all cytokines showed a different segregation between intervention and non-intervention groups, with IL-6/TNF-α and IL-6/IL-17A associated, respectively. Besides that, the echo score of mitral involvement had a negative correlation with IL-17A, showing that the lower the interleukin serum concentration, the higher the valve damage.
Conclusions: Patients with severe rheumatic MV disease had a more intense inflammatory response evidenced by high concentrations of inflammatory cytokines, as compared to asymptomatic patients with stable MV disease. The interleukin IL-17A may play a role on the regulation of the inflammatory response on RHD.