Inhaled Nitric Oxide Therapy Fails to Improve Outcome in Experimental Severe Influenza

Darwish, Ilyse; Miller, Chris; Kain, Kevin C.; Liles, W. Conrad

Nitric oxide (NO) is an important cellular signalling molecule synthesized from L-arginine by NO synthase (NOS). There are three types of NOS: constituent and calcium-dependant isoforms that are principally present in endothelial and neuronal cells (eNOS and nNOS, respectively), and the inducible or Ivyspring International Publisher calcium-independent isoform, iNOS (16) . In the airways, NOS is present in a variety of cells, including macrophages, vascular endothelial cells, airway epithelial cells and neurons where NOS activity is known to mediate neurotransmission, smooth muscle contraction and mucin secretions. NO is also a well known biological mediator in the host response to infection (16, 17) . Various inflammatory stimuli such as LPS and cytokines including IFNg and TNF can cause high and sustained NO production by iNOS; depending on the species, strain, infection dose and pathogen entry route, iNOS activity can result in proor anti-inflammatory responses, cytotoxicity, or cytoprotection [reviewed in (16) ].