New IL-1 family IL-38 is highly expressed in alveolar cells of drug-induced lung injury and idiopathic pulmonary fibrosis

Objectives: The newly characterized cytokine IL-38 is a member of the IL-1 family but its action remains unknown. In order to clarify the function of IL-38, we examined its immunohistochemical expression in several types of interstitial lung disease (ILD). Methods: We generated an anti-human IL-38 monoclonal antibody (clone H127C) and used it to immunohistochemically examine the expression of IL-38 protein in lung tissues obtained from 12 patients with idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP), 5 with acute exacerbation of IPF, 10 with drug-induced ILD, and 22 control subjects. Results: IL-38 protein was not strongly expressed in pulmonary alveolar tissues in all of the 22 control subjects. In contrast, IL-38 was overexpressed in the lungs of 4/5 (80%) patients with acute exacerbation of IPF and all (10/10, 100%) of the patients with drug-induced ILD. It was noteworthy that IL-38 overexpression was limited to hyperplastic type II pneumocytes, which are considered to reflect regenerative change following diffuse alveolar damage in ILD. Conclusions: Our present findings indicate that IL-38 protein is overexpressed in areas of local inflammation in some forms of acute lung injury such as drug-induced ILD and acute exacerbation of IPF. IL-38 may regulate the process of regeneration and acute and/or chronic deterioration in ILDs.