Regulation of inflammatory responses to Bordetella pertussis by N-G-monomethyl-L-arginine in mice intranasally infected

To investigate effect of MMLA, an inhibitor of nitric oxide (NO) production , on regulation of inflammatory responses to Bordetella pertussis infection , mice were infected intranasally, and treated with various concentrations of MMLA. Ten days after infection, mice treated with MMLA at dosage of 100 mg/kg, given intraperitoneally in a single dose or for 5 consecutive days, showed at histopathologic examination, a significant decrease of intensity of inflammation (scores, 0.6 +/- 0.2 and 0.9 +/- 0.5 respectively). A decre ase of cellular accumulation of neutrophils and lymphocytes in the bronchoa lveolar lavage (BAL) fluid was observed in infected mice treated with MMLA, especially at dosage of 10 mg/kg, given in a single dose intraperitoneally , In addition, BP-infected mice treated with MMLA (100 mg/kg, intraperitone ally) for 5 consecutive days showed higher mortality rate than untreated mi ce infected with B. pertussis, and the number of B. pertussis in lungs of m ice treated with MMLA was significantly increased. However, MMLA treatment of infected mice had some effect on levels of IFN-gamma and nitrite/nitrate (end-stable products of NO) in the BAL fluid. This study indicates that NO may play a role either as microbiocidal agent or as a modulator of immune regulation, inasmuch as it may upregulate tissue inflammatory response to B , pertussis.