Interleukin-33 in systemic sclerosis: correlation with clinical manifestations and disease subset

Abstract

Background Systemic sclerosis (SSc) is a generalized connective tissue disorder characterized by sclerotic changes in the skin and internal organs. Interleukin-33 (IL-33) is a newly reported cytokine of the IL-1 family. Aim of the work The aim of this study was to determine serum levels of IL-33 in SSc patients and evaluate its association with clinical manifestations and disease subset. Patients and methods The patients in this study were divided into group A and group B. Group A included 30 adult patients with SSc, which was subdivided into diffuse systemic sclerosis (dSSc) and limited systemic sclerosis (lSSc). All cases were diagnosed according to the American College of Rheumatology criteria for SSc. Group B included 15 healthy adults (age and sex matched) who served as controls. Serum IL-33 levels were examined by means of enzyme-linked immunosorbent assay in 30 patients with SSc and in 15 healthy individuals. Skin assessment was done using the modified Rodnan skin score. Results IL-33 was increased in all SSc patients compared with controls. The levels of IL-33 were significantly higher in the dSSc subset compared with the lSSc subset. IL-33 is highly correlated to the presence of pulmonary fibrosis, Raynaud’s phenomenon, pitting scars and ulcers, pulmonary hypertension, joint contracture, and modified Rodnan skin score. Thus, IL-33 levels were increased in SSc patients and correlated with the extent of skin sclerosis and the severity of pulmonary fibrosis. Therefore, IL-33 possibly plays a role in cutaneous and pulmonary fibrosis in SSc patients. Conclusion IL-33 may have a significant role in the pathogenesis of SSc. IL-33 serum levels paralleled the severity of the disease subset. Understanding of IL-33 functions is important for the development of new therapeutic approaches including IL-33 inhibitors and IL-33 receptor blockers as a therapeutic target.