Relevance of interferon-gamma in pathogenesis of life-threatening rapidly progressive interstitial lung disease in patients with dermatomyositis

Dermatomyositis (DM) with rapidly progressive interstitial lung disease (DM RP-ILD) is a life-threatening condition. Serum cytokine levels are potentially suitable biomarkers for DM RP-ILD. However, the relationships among cytokine levels, lung imaging findings, and lung pathology have not been investigated. The

Our results suggest strong IFN-γ-related immune reaction in the lungs and hilar lymph nodes of patients with life-threatening DM RP-ILD, and potential IFN-γ involvement in the pathogenesis of DM, specifically in the pulmonary lesions of RP-ILD.

The study subjects were nine patients with life-threatening DM RP-ILD and severe hypoxemia (partial arterial oxygen pressure (PaO2)/fraction of inspired oxygen (FiO2) ratio ≤ 200) before receiving intensive care management, who were admitted to our hospital between 2006 and 2015. The controls included 10 patients with DM without RP-ILD and 19 healthy subjects. We assessed the association between serum cytokine levels and computed tomography (CT) scores of the lung (ground glass opacity-score, G-score; fibrosis-score, F-score). Lung, hilar lymph nodes, and spleen from two autopsies were examined by hematoxylin-eosin (H&E) staining and immunostaining.

Serum interferon (IFN)-γ, interleukin (IL)-1β and IL-12 levels were significantly higher in patients with DM RP-ILD than in the other two groups, whereas serum IL-6 levels were elevated in the two patient groups but not in the healthy subjects. Serum levels of IL-2, IL-4, IL-8, IL-10, IFN-α, and TNF (tumor necrosis factor)-α were not characteristically elevated in the DM RP-ILD group. Serum IFN-γ levels correlated with G-scores in patients with DM RP-ILD, while IL-1β was negatively correlation with F-scores. Immunohistochemical staining showed infiltration of numerous IFN-γ-positive histiocytes in the lung and hilar lymph nodes; but not in the spleen. Serum IL-6 levels did not correlate with the CT scores. Numerous IL-6-positive plasma cells were found in hilar lymph nodes, but not in the lungs or spleen. Conclusions: Our results suggest strong IFN-γ-related immune reaction in the lungs and hilar lymph nodes of patients with life-threatening DM RP-ILD, and potential IFN-γ involvement in the pathogenesis of DM, specifically in the pulmonary lesions of RP-ILD.