The Role of Interleukin-13 in Patients with Rheumatic Valvular Fibrosis: A Clinical and Histological Study.

Interleukin (IL)-13 is a major inducer of fibrosis in many chronic infectious diseases, yet few studies have reported its role in valvular fibrosis in patients with rheumatic heart disease (RHD). The study aim was to investigate the role of IL-13 in mitral valvular fibrosis in patients with RHD. Peripheral blood samples were collected from surgical patients with RHD (n = 18) and from healthy controls (n = 9). Serum levels of IL-13 and interferon (IFN)-gamma were analyzed using ELISA. Rheumatic mitral valves removed from surgical patients with RHD, and normal mitral valves, were obtained at autopsy. The expression and distribution of collagen I, collagen III, and IL-13Ralpha1 were examined by immunohistochemical staining, the degree of which was measured using computed imaging analysis. Higher IL-13 levels were observed in RHD patients (15.16 +/- 9.62 pg/ml; p < 0.05) than in healthy controls (7.78 +/- 3.87 pg/ml). RHD patients had high levels of IFN-gamma (9.95 +/- 0.77 pg/ml; p <0.05) compared to healthy controls (5.95 +/- 0.69 pg/ml). Immunohistochemistry showed that, compared to normal valves, rheumatic mitral valves expressed high levels of collagen I (0.01931 +/- 0.00159 versus 0.01183 +/- 0.00207; p < 0.05), collagen III (0.00726 +/- 0.00078 versus 0.00342 +/- 0.00124; p <0.05), and IL-13Rcxl (0.00454 +/- 0.00086 versus 0.00017 +/- 0.00008; p <0.01). Collagens I and III were each expressed in heart interstitial cells, while IL-13Ralpha1 was expressed in the endothelial cells and smooth muscle cells of the blood vessels, and in interstitial cells. Patients with RHD showed increased serum levels of IL-13 compared to healthy controls. IFN-gamma levels were clearly different among RHD patients and healthy controls. The expression of collagens I and III and IL-13Ralpha1 was higher in rheumatic mitral valves compared to normal mitral valves. IL-13 may induce mitral valvular fibrosis in RHD.