Aberrant expression of cytokine interleukin 9 along with interleukin 4 and interferon γ in connective tissue disease-associated interstitial lung disease: association with severity of pulmonary fibrosis

Abstract

Introduction: Connective tissues diseases (CTDs) are a heterogeneous group of disorders that share certain clinical characteristics and disturbed immunoregulation. Interstitial lung diseases (ILDs), also known as diffuse parenchymal lung diseases, are among the most serious pulmonary complications associated with CTDs. Interleukin 9 (IL-9), IL-4 and interferon γ (IFN-γ) - cytokines with important roles in autoimmune disease - were studied in CTD patients and CTD-ILD patients.

Material and methods: Sixty-one hospitalized untreated CTD patients were recruited, and 20 healthy volunteers were enrolled as controls. The 61 CTD patients were divided into a simple CTD group and a CTD-ILD group, and the plasma protein IL-9, IL-4 and IFN-γ levels were measured by enzyme-linked immunosorbent assay (ELISA).

Results: The results indicate that the serum IL-9 levels were significantly higher in CTD-ILD and simple CTD patients than they were in healthy controls (each p < 0.05) and that the levels were elevated in CTD-ILD patients compared with simple CTD patients (p < 0.05). The IL-4 levels were higher in CTD-ILD patients than they were in the simple CTD patients (p < 0.05) and healthy controls (p < 0.01). In addition, the serum IL-9 levels were negatively correlated with the level of IFN-γ (r (2) = 0.34, p = 0.01), the estimated percentage of predicted forced vital capacity (FVC%) (r (2) = 0.36, p = 0.00) and the estimated percentage of predicted diffusing capacity (DLCO%) (r (2) = 0.27, p = 0.04) and were positively correlated with the IL-4 level (r (2) = 0.31, p = 0.01).

Conclusions: Interleukin-9 may play an important role in the pathogenesis of CTD and may contribute to the progression of interstitial lung injury in CTD patients.

Keywords: connective tissues disease; interferon γ; interleukin 4; interleukin 9; interstitial lung disease.

Figure 1

Serum IL-9 protein levels. The serum IL-9 levels in each group, including CTD-ILD patients (CTD-ILD group, n = 29), simple CTD patients (simple CTD group, n = 32) and healthy controls (HC, n = 20), were detected by a specific ELISA. Bars indicate the mean values ± SD in each group. The serum IL-9 levels were significantly higher in CTDILD and simple CTD patients compared to healthy controls (p < 0.05 for each) and were elevated in CTD-ILD patients compared to simple CTD patients (p < 0.05)

Figure 2

Serum IL-4 protein levels. The serum IL-4 levels were higher in CTD-ILD patients (CTD-ILD group, n = 29) compared to simple CTD patients (simple CTD group, n = 32) and healthy controls (HC, n = 20) (p < 0.05; p < 0.01). The serum IL-4 levels were significantly increased in simple CTD patients compared to healthy controls (p < 0.05). Bars represent the mean values ± SD

Figure 3

Serum IFN-γ protein levels. This figure shows that the serum IFN-γ protein levels were lower in CTD-ILD patients (CTD-ILD group, n = 29) compared to simple CTD patients (simple CTD group, n = 32) (p < 0.05) and that the serum IFN-γ levels were higher in simple CTD patients compared to healthy controls (HC, n = 20) (p < 0.05). There was no significant difference between the CTD-ILD group and healthy controls (p > 0.05)