Nitric oxide levels in exhaled air and inducible nitric oxide synthase immunolocalization in pulmonary sarcoidosis

Abstract

Cytokines such as tumour necrosis factor-alpha and interferon gamma are associated with active pulmonary inflammation in sarcoidosis and they upregulate inducible nitric oxide synthase (iNOS). The objectives of this study were to examine iNOS upregulation in sarcoidosis by showing raised exhaled nitric oxide and increased iNOS activity in lung biopsy specimens of these patients utilizing immunohistochemistry. Exhaled NO was measured by a chemiluminescence analyser in 12 patients with newly diagnosed biopsy-proven sarcoidosis before and after 6 weeks of corticosteroid therapy. Lung biopsy specimens from these patients were subjected to immunohistochemical staining with a specific iNOS antibody. Exhaled NO was raised in newly diagnosed sarcoidosis (mean+/-SEM): 9.8+/-0.4 versus 4.1+/-0.2 parts per billion (ppb) in 21 healthy controls, p<0.001; and fell significantly after 6 weeks treatment with corticosteroids to 5.9+/-1.4 ppb; p<0.01. There was no correlation between exhaled NO and other markers of disease activity. Immunohistochemical staining demonstrated iNOS activity in respiratory epithelium and granulomas in patients with sarcoidosis. Exhaled nitric oxide is raised in patients with active pulmonary sarcoidosis and may be a result of inducible nitric oxide synthase upregulation. The fall in exhaled nitric oxide following corticosteroid therapy may reflect inhibition of inducible nitric oxide synthase in the respiratory epithelium and granulomas.