Acute inhibition of nitric oxide exacerbates airway hyperresponsiveness, eosinophilia and C-C chemokine generation in a murine model of fungal asthma

Objective and Design: This study examined he role of nitric oxide in change s in airway physiology and inflammation in a murine model of fungal allergy induced by Aspergillus fumigatus (A. fumigatus) by treatment of A. fumigat us-sensitized mice with NG-nitro-L-arginine methyl ester (L-NAME) or D-NAME (8 mg/kg; i.p.). Materials and Methods: Female CBA/J mice received A. fumigatus antigen diss olved in incomplete Freund's adjuvant (10 mg/100 mi i.p. and s.c.) followed 2 weeks later by A. fumigatus antigens (20 mg; i.n.) and a subsequent i.t. challenge 4 days later. Airway physiology and inflammation were examined ( 24 to 72 h) following i.t, challenge. Results: L-NAME-treated mice had lower lung nitrite levels 24 h after A, fu migatus challenge, but higher airway hyperresponsiveness and inflammation c ompared to D-NAME controls. Airway inflammation in the L-NAME treatment gro up (72 h) was characterized by a greater bronchoalveolar lavage (BAL), peri bronchial eosinophilia and augmented levels of CC chemokines compared to co ntrols. Conclusions: These findings suggest that nitric oxide is an important modul ator of airway hyperresponsiveness, inflammation and C-C chemokine generati on during allergic airway responses to A. fumigatus.