Th-17 cytokines and interstitial lung involvement in systemic sclerosis

Abstract

The two phenotypes of both limited and diffuse systemic sclerosis (SSc) have different forms of pulmonary involvement: pulmonary arterial hypertension (limited phenotype) or interstitial lung disease (ILD) (diffuse phenotype). We aimed to investigate whether Th17-related cytokines, as measured in exhaled breath condensate (EBC) and in serum were connected to ILD in diffuse SSc patients. We found that for both limited and diffuse SSc, the EBC levels of all cytokines and most of the cytokine serum levels were significantly higher in patients than in controls, while, the EBC levels of Th-17 cytokines and the serum levels of IL-10 and TNF-α were significantly higher in diffuse than in limited SSc. Moreover, the thoracic CT-scan score of ILD was significantly associated with the EBC levels of IL-1 beta and with the serum IL-23, TNF-α and IL-10 levels, whereas lung carbon monoxide diffusing capacity was negatively related to the EBC levels of IL-1 beta, IL-17 and serum IL-10. Serum IL-23 was also inversely correlated with vital capacity. In conclusion, in diffuse SSc patients our results show a clear link between Th-17 cytokines measured both in EBC and in serum with interstitial lung involvement. This highlights how important it is to target Th-17 cytokines when developing new treatments for lung fibrosis.

Serum interleukin‐34 levels in patients with systemic sclerosis: Clinical association with interstitial lung disease

“…Another important pathological aspect of IL‐34‐induced macrophages is to convert memory T cells into T‐helper (Th)17 cells, which are increased in the skin and peripheral blood of SSc patients and associated with the disease activity . Especially, the levels of Th17 cytokines such as IL‐17 and IL‐23 in the peripheral blood and exhaled breath condensate are positively correlated with ILD severity in SSc patients . Considering the positive correlation between serum IL‐34 levels and the severity of ILD in SSc patients, IL‐34 may enhance Th17 cells in SSc, contributing to the development of ILD.…”

“…14 Especially, the levels of Th17 cytokines such as IL-17 and IL-23 in the peripheral blood and exhaled breath condensate are positively correlated with ILD severity in SSc patients. 15 Considering the positive correlation between serum IL-34 levels and the severity of ILD in SSc patients, IL-34 may enhance Th17 cells in SSc, contributing to the development of ILD.…”

IL-17 and Th17 cells in systemic sclerosis: a comprehensive review

“…Although there were no differences reported between Th17 cell count from bronchoalveolar fluid between patients with and without pulmonary fibrosis [36], IL-17A was higher in exhaled breath concentrate from diffuse Ssc patients when compared to healthy controls and limited Ssc patients. Also IL-17A from the exhaled breath concentrate inversely correlated with DLCO values [37]. Molecular profiling of lung tissue using microarray mRNA expression studies proved that pulmonary hypertensive derived fibroblasts had higher expression for IL-17, IL-6 and IL-8 expressed genes [38].…”

Interstitial lung disease in Systemic sclerosis: insights into pathogenesis and evolving therapies

“…11 However, in exhaled breath of SSc-ILD patients, there was increased TNF-α, TGF-β, IL-17 and IL-23; possibly implying a possible local role of this axis in the pathogenesis of fibrosis. 12…”