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PEDIATRICS Vol. 105 No. 5 May 2000, pp. 1013-1019

Diminished Inducible Nitric Oxide Synthase Expression in Fulminant Early-Onset Neonatal Pneumonia

Received May 3, 1999; accepted Sep 29, 1999.

Outi Aikio*, §, Katri VuopalaDagger , parallel , Marja-Leena Pokela, and Mikko Hallman*, §, #

From the Departments of * Pediatrics and Dagger  Pathology and § Biocenter Oulu, University of Oulu, Oulu, Finland; parallel  Department of Pathology, Central Hospital of Lapland, Rovaniemi, Finland;  Division of Neonatology, Department of Pediatrics, Oulu University Hospital, Oulu, Finland; and # Division of Neonatal Medicine, University of California Irvine, Irvine, California.

Objective.  Fulminant early-onset neonatal pneumonia is associated with ascending intrauterine infection (IUI), prematurity, persistent pulmonary hypertension (PPHN), and septicemia. Nitric oxide (NO) as an inflammatory mediator is included in antimicrobial defense and has a role in pathogenesis of septic shock. The aim was to study the role of inflammatory NO in neonatal pneumonia.

Methods.  Lungs from 36 autopsies were studied: 12 had fulminant early-onset neonatal pneumonia, 5 pneumonia of later onset, and 19 controls had similar gestational and postnatal age. In addition, airway specimens from 21 intubated newborns were analyzed: 7 with fulminant early-onset pneumonia, 7 apparently noninfected infants born prematurely attributable to IUI, and 7 premature infants of similar gestation. Specimens were analyzed for inducible NO synthase (NOS2) and nitrotyrosine, an indicator of NO toxicity. The degree of staining was analyzed.

Results.  In fulminant pneumonia, alveolar macrophages (AM) showed significantly less NOS2 immunoactivity than the controls. In the airway specimens, the infants with fulminant pneumonia 0 to 2 days after birth had significantly lower intracellular NOS2 and nitrotyrosine and significantly lower interleukin-1beta and surfactant protein-A than apparently noninfected IUI infants. NOS2 and the other indices increased significantly during the recovery.

Conclusions.  For the first time, we report NOS2 expression by macrophages from human neonates. In fulminant early-onset neonatal pneumonia, delayed production rather than excess of pulmonary inflammatory NO is associated with severe symptoms.  Key words:  immunohistochemistry, immunity, newborn, nitric oxide, nitric oxide synthase, nitrotyrosine, pneumonia.


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