Abstract

ObjectiveSystemic sclerosis (SSc) mortality is extremely variable in its internal organ involvement. Pulmonary fibrosis occurs in up to 30% of the cases. Animal models provide evidence that IL-33 is able to induce both cutaneous and pulmonary fibrosis via increased IL-13 and in SSc patients the levels of IL-33 correlate with skin fibrosis. Our aim was to test whether both IL-33 and IL-13 are higher in patients with diffuse SSc and interstitial lung disease (SSc-ILD) compared to SSc patients without ILD and healthy controls.MethodsSerum levels of IL-13 and IL-33 were measured in 30 SSc patients with diffuse disease and 30 healthy controls by enzyme-linked immunosorbent assay. The extent of pulmonary fibrosis was assessed according to HRCT Warrick score. Pulmonary function tests included lung diffusion capacity for carbon monoxide, forced vital capacity and total lung capacity.ResultsBoth IL-13 and IL-33 levels were increased in SSc patients compared to controls and significantly associated each other. DLco, FVC and TLC scores were inversely associated with IL-33 and IL-13 levels. Both IL-33 and IL-13 levels were significantly associated with the Warrick severity score and higher in the group of SSc patients with reduced pulmonary function compared to SSc patients with normal pulmonary function tests.ConclusionThe IL-13/IL-33 axis needs to be further explored in longitudinal studies of SSc-ILD patients to assess its validity as a biomarker and future treatment target, as does downstream mediator ST2.

Highlights

  • Systemic sclerosis (SSc) is a connective tissue disease characterized by the triad of microvascular injury, immunologic activation and fibrosis [1]

  • We found that IL-13 and IL-33 levels were significantly higher in SSc patients compared to controls

  • We observed that IL-13 and IL-33 are directly correlated with one another (r2 = 0.32, p = 0.0009)

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Summary

Introduction

Systemic sclerosis (SSc) is a connective tissue disease characterized by the triad of microvascular injury, immunologic activation and fibrosis [1]. The clinical phenotype of the disease differs widely. It is crucial to apply strict patient selection criteria to identify effective treatments for life-threatening organ complications, thereby addressing one of the main clinical unmet need in SSc research [2]. The pathogenesis of SSc needs to be clarified, previous studies confirm that some cytokines and growth factors influence fibrosis progression in SSc by stimulating the activation of fibroblasts, impairing endothelial cells activity, and altering immune system function [4, 5]. We focused our attention in particular to IL-13 and IL-33, in light of the growing body of recent evidence suggesting a possible role for these cytokines in fibrogenesis

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