Nitric oxide regulation of asthmatic airway inflammation with segmental allergen challenge

Background: Despite evidence of increased nitric oxide (NO) in asthmatic co mpared with healthy individuals, the role of NO in airway inflammation is u nclear. Objective: The purpose of the study was to determine the in vivo effects of localized allergen challenge on airway NO levels and transcription factor activation. Methods: In this study localized allergen challenge was used as a model of asthmatic excerbation to determine the relationship of NO to airway inflamm ation. Results: With allergen challenge, asthmatic patients had a rise in airway K O levels, whereas NO levels in healthy controls did not change. The Increas ed NO in asthma with allergen challenge compared with healthy control subje cts was associated with an increase in inflammatory cytokines (GM-CSF and m acrophage inflammatory protein-1) in epithelial lining fluid and eosinophil ic infiltrate in bronchoalveolar lavage fluid (BAL) and biopsy specimens. T o investigate the mechanisms of cytokine gene expression, activation of the transcription factors activator protein-1 and nuclear factor-kappa B (NF-k appa B) in cells from BAL were evaluated. Activator protein-1 was not activ ated before or after local allergen challenge. In contrast, NF-kappa B acti vation was less in BAL, cells from asthmatic patients with increased NO in comparison with controls. Conclusion: Our studies are the first to suggest an inverse correlation bet ween NF-kappa B and airway KO in a localized segmental allergen challenge m odel in allergic asthmatic patients. The current study demonstrates that ac tivation of the inflammatory response (eg, cytokines, cellular infiltrate) in allergic asthmatic patients is temporally associated with increased airw ay NO. We propose that NO that is up-regulated by cytokines is part of an a utoregulatory feedback loop (ie, allergen challenge stimulates inflammatory cytokine production, which in turn stimulates NO production, and NO down-r egulates cytokine production).