Received for publication April 6, 2004.
Revised June 29, 2004.
Accepted for publication June 29, 2004.

Nitric oxide as a non-invasive biomarker of LPS induced airway inflammation: Possible role in lung neutrophilia

Abstract

LPS is known to generate nitric oxide (NO) in the airway through the activation of nitric oxide synthase (NOS). The functional consequences of this on the inflammatory response are not clear, with conflicting data published. In the clinic exhaled NO (exNO) is used as a non-invasive biomarker to assess the extent of airway inflammation. It is proposed that monitoring levels of exNO could be a useful guide to determining the effectiveness of disease modifying therapies. The aim was, using pharmacological tools, to determine the role of NO in an aerosolised LPS driven animal model of airway inflammation by assessment of exNO, neutrophilia and inflammatory biomarkers, using a non selective NOS inhibitor, L-NAME and a selective iNOS inhibitor, 1400W. Real time mRNA analysis of the lung tissue indicated an increased gene expression of iNOS following LPS challenge with minimal impact on constitutive NOS isoforms. LPS induced an increase in exNO which appeared to correlate with the increase in iNOS gene expression and airway neutrophilia. Treatment with L-NAME and 1400W resulted in comparable reductions in exNO, a reduction in airway neutrophilia but had little impact on a range of inflammatory biomarkers. This study indicates that the LPS-induced rise in exNO is due to enhanced iNOS activity and that NO has a role in airway neutrophilia. Additionally, it appears using exNO as a guide to monitoring airway inflammation may have some use but data should be interpreted with caution when assessing therapies that may directly impact on NO formation.

Key words: Lipopolysaccharide, Lung, NOS inhibitors, Neutrophilia, Nitric oxide, Rats

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