Type 2 cytokines and scleroderma interstitial lung disease

Abstract

Interstitial lung disease (ILD) is a life-threatening complication of systemic sclerosis (SSc). Type 2 (Th2) cytokines play a pivotal role in airway disease. Study aim was to evaluate serum level of Th2 interleukin (IL) and chemokine in SSc-ILD. Serum levels of IL-4, IL-5, IL-11, IL-13, IL-21, IL-31 and CXCL-13 were measured by Bio-Plex Multiplex Immunoassays in 60 SSc patients and 20 healthy controls (HC). Pulmonary function tests with diffusion lung capacity for carbon monoxide (DLco) and high resolution computed tomography (HRCT) were performed in SSc patients. ILD is defined as fibrotic changes (ground glass, reticular and honeycombing), assessed by Computer-Aided Lung Informatics for Pathology Evaluation and Ratings (CALIPER) software, affecting at least 10% of the lungs. Serum levels of Th2 cytokines were higher in SSc patients than HC. A linear correlation was observed between ground glass and IL-13 (r = 0.342, p < 0.01), IL-21 (r = 0.345, p < 0.01), IL-31 (r = 0.473, p < 0.001), IL-4 (r = 0.863, p < 0.001), IL-5 (r = 0.249, p < 0.05) and peripheral blood eosinophils (r = 0.463, p < 0.001). We found a negative correlation between DLco and IL-4 (r = - 0.511, p < 0.001) and peripheral blood eosinophils (r = - 0.446, p < 0.001). In the logistic regression analysis, IL-4 is associated with DLco ≤ 60% of the predicted [OR 1.039 (CI 95%: 1.015-1.064), p < 0.001], whilst mRSS [OR 1.138 (CI 95%: 1.023-1.266), p < 0.05] and IL-4 [OR 1.017 (CI 95%: 1-1.034), p < 0.05] were associated with ILD. Th2 inflammation could play a key role in early phase of SSc-ILD.

Keywords: CALIPER; Ground glass; Interstitial lung disease; Systemic sclerosis; Th2 cytokines.

Fig. 1

Bivariate correlations between Th2 cytokines serum levels and radiological patterns of interstitial lung disease (ILD), assessed through CALIPER software, in systemic sclerosis (SSc) patients. A: Positive linear correlation between IL-4 and ground glass (r = 0.863, p < 0.001); B: Positive linear correlation between IL-31 and ground glass (r = 0.473, p < 0.001); C: Positive linear correlation between IL-21 and ground glass (r = 0.345, p < 0.01); D: Positive linear correlation between IL-13 and ground glass (r = 0.342, p < 0.01); E: Positive linear correlation between IL-5 and ground glass (r = 0.249, p < 0.05); F: Negative linear correlation between IL-4 and honeycombing (r =  − 0.281, p < 0.05)

Fig. 2

Bivariate correlations between Th2 cytokines serum levels and diffusing capacity of lung for carbon monoxide (DLco) in systemic sclerosis (SSc) patients. A: Negative linear correlation between IL-4 and DLco (r =  − 0.511, p < 0.001); B: Negative linear correlation between IL-5 and DLco (r =  − 0.259, p < 0.05); C: Negative linear correlation between IL-31 and DLco (r =  − 0.258, p < 0.05)

Fig. 3

Peripheral blood eosinophil count in systemic sclerosis (SSc) patients and its association with variables of interstitial lung disease (ILD). A: Positive linear correlation between peripheral blood eosinophil count and ground glass CALIPER pattern (r = 0.463, p < 0.001); B: N egative linear correlation between peripheral blood eosinophil count and diffusing capacity of lung for carbon monoxide (DLco) (r =  − 0.446, p < 0.001); C: Comparative analysis of the percentage of ground glass parenchyma between systemic sclerosis (SSc) patients with peripheral blood eosinophils ≥ 150/μl and SSc patients with peripheral blood eosinophils < 150/μl (p < 0.05)