Interleukin-17 and interleukin-23: importance in the pathogenesis of lung impairment in patients with systemic sclerosis

Abstract

Aim: T cell abnormalities with a focus on Th17 cells have been associated with the pathogenesis of systemic sclerosis (SSc) and interstitial lung disease (ILD). The aim of this study was to evaluate serum levels of interleukin (IL)-17, IL-21 and IL-23 in SSc patients and to assess their relationship with ILD-SSc.

Methods: Thirty-eight patients with SSc and 39 healthy controls were recruited. Serum IL-17, IL-21 and IL-23 levels were examined using enzyme-linked immunosorbent assay (ELISA). Lung involvement of SSc patients was assessed functionally (diffusing capacity of the lung for carbon monoxide [DLCO], body plethysmography) and radiologically (using average disease extent on high resolution computed tomography [HRCT] of the lungs according to the percentage of interstitial changes and quantified with a 30-point Warrick score) in 29 SSc patients.

Results: Serum IL-17 and IL-23 levels were significantly decreased and IL-21 levels were elevated in SSc patients when compared with controls (P < 0.001, P < 0.001, P < 0.01, respectively). The level of IL-17 was negatively associated with disease duration (P = 0.01) and positively with HRCT Warrick score (P = 0.03). IL-23 concentration negatively correlated with DLCO (P = 0.04), total lung capacity (TLC) (P = 0.01) and the 6-min walk test distance (P = 0.03). No associations were found between the cytokine levels and the average extent of the disease on HRCT.

Conclusion: While the relationship between Th17-associated cytokines and ILD-SSc needs to be verified in a larger cohort of patients, the changes in concentrations of IL-17, IL-21 and IL-23 support the hypothesis that these cytokines may play a role in the pathogenesis of SSc.

Keywords: interleukin-17; interleukin-21; interleukin-23; interstitial lung disease; systemic sclerosis.