Diminished inducible nitric oxide synthase expression in fulminant early-onset neonatal pneumonia

Objective. Fulminant early-onset neonatal pneumonia is associated with asce nding intrauterine infection (IUI), prematurity, persistent pulmonary hyper tension (PPHN), and septicemia. Nitric oxide (NO) as an inflammatory mediat or is included in antimicrobial defense and has a role in pathogenesis of s eptic shock. The aim was to study the role of inflammatory NO in neonatal p neumonia. Methods. Lungs from 36 autopsies were studied: 12 had fulminant early-onset neonatal pneumonia, 5 pneumonia of later onset, and 19 controls had simila r gestational and postnatal age. In addition, airway specimens from 21 intu bated newborns were analyzed: 7 with fulminant early-onset pneumonia, 7 app arently noninfected infants born prematurely attributable to IUI, and 7 pre mature infants of similar gestation. Specimens were analyzed for inducible NO synthase (NOS2) and nitrotyrosine, an indicator of NO toxicity. The degr ee of staining was analyzed. Results. In fulminant pneumonia, alveolar macrophages (AM) showed significa ntly less NOS2 immunoactivity than the controls. In the airway specimens, t he infants with fulminant pneumonia 0 to 2 days after birth had significant ly lower intracellular NOS2 and nitrotyrosine and significantly lower inter leukin-1 beta and surfactant protein-A than apparently noninfected IUI infa nts. NOS2 and the other indices increased significantly during the recovery . Conclusions. For the first time, we report NOS2 expression by macrophages f rom human neonates. In fulminant early-onset neonatal pneumonia, delayed pr oduction rather than excess of pulmonary inflammatory NO is associated with severe symptoms.