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

Cytokines such as tumour necrosis factor-a and interferon gamma are associa ted with active pulmonary inflammation in sarcoidosis and they upregulate i nducible 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 patient s 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 cort icosteroid therapy. Lung biopsy specimens from these patients,were subjecte d 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 m arkers of disease activity. Immunohistochemical staining demonstrated iNOS activity in respiratory epithelium and granulomas in patients with sarcoido sis. Exhaled nitric oxide is raised in patients with active pulmonary sarcoidosi s and may be a result of inducible nitric oxide synthase upregulation. The fail in exhaled nitric oxide following corticosteroid therapy may reflect i nhibition of inducible nitric oxide synthase in the respiratory epithelium and granulomas.