interleukin-8 and Persistent-Fetal-Circulation-Syndrome

The aim of this study was to determine the effects of inhaled NO with different oxygen concentrations on the inflammatory cascade in newborns with hypoxic respiratory failure secondary to persistent pulmonary hypertension.. 60 newborns received iNO and 30 of them received an initial oxygen concentration of 45% (group 1), while the other 30 newborns received an initial oxygen concentration of 80% (group 2). The levels of inflammatory cytokines (IL-6, IL-8, TNF-α) were measured. The clinical outcome was also recorded.. The findings show that interleukin concentrations (IL-6, IL-8, TNF-α) were significantly decreased between 0 and 72 hours (p < 0.01) in the newborns exposed to initial oxygen concentration of 45% and significantly increased in the other group.. When inhaled, NO was co-administered with concentration of O(2) <45%, anti-inflammatory responses occurred, in accord with evidence in the published literature. The benefits of iNO on the clinical outcome in the current study demonstrate that inhaled NO in both groups was associated with improved short-term oxygenation.

Topics: Administration, Inhalation; Dose-Response Relationship, Drug; Female; Humans; Infant, Newborn; Interleukin-6; Interleukin-8; Male; Nitric Oxide; Oxidative Stress; Oxygen; Persistent Fetal Circulation Syndrome; Respiration, Artificial; Respiratory Distress Syndrome, Newborn; Tumor Necrosis Factor-alpha

The peptide endothelin-1 (ET-1) plays an unknown role in the pathogenesis and progression of two important neonatal pulmonary disorders, chronic lung disease (CLD) of prematurity and persistent pulmonary hypertension of the newborn (PPHN). Inhaled nitric oxide (INO) is a proven vasodilator therapy in PPHN and is an experimental therapy in CLD. We sought to determine the effects, if any, of the interaction of inhaled INO with ET-1 in these two separate disorders. Infants (n=21) with PPHN (mean gestation age, 39.4 weeks; mean birth weight, 3470 g) were treated with INO. All infants were <72 h of age at baseline. Plasma obtained at baseline and after 24 h of INO therapy was assessed for ET-1. The change in ET-1 levels with INO was inversely correlated with change in arterial partial pressure of O(2) (r=-0.71, P=0.0003). A separate group of 33 patients with CLD (mean gestational age, 27 weeks; mean birth weight, 740 g; mean age, 19 days) had tracheal aspirate levels of ET-1 obtained before, during, and after 7 days' administration of INO. Values were normalized by soluble secretory component of IgA. Tracheal aspirate ET-1 levels were detectable before INO therapy. There was no significant change during or after treatment with INO. There was not a significant correlation between baseline fractional inspired O(2) and ET-1 levels. There was a non-significant trend in the correlation between the change in ET-1 and the change in interleukin-8 levels in tracheal aspirate. This report confirms the presence of ET-1 in tracheal aspirate of premature infants who are developing CLD and reaffirms the presence of ET-1 in plasma of infants with PPHN. Short-term INO therapy was associated with a decrease in plasma ET-1 levels in PPHN, but did not affect tracheal aspirate ET-1 in CLD. Given the vasconstrictive, profibrotic, and proinflammatory properties of ET-1, specific ET-1 receptor antagonists could be considered as candidates for trials as adjunct therapy in either or both of these disorders.

Topics: Administration, Inhalation; Biomarkers; Endothelin-1; Humans; Hypertension, Pulmonary; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Interleukin-8; Nitric Oxide; Persistent Fetal Circulation Syndrome; Pulmonary Disease, Chronic Obstructive