Effects of inhaled beclomethasone compared to systemic dexamethasone on lung inflammation in preterm infants at risk of chronic lung disease.

The purpose of this study was to compare the effects of daily inhaled beclomethasone (3 x 500 microg) started on day 3 of life, with that of systemic dexamethasone (0.5 mg/kg/day) started between days 11-13 on clinical variables, lung inflammation, and pulmonary microvascular permeability in preterm infants at risk for chronic lung disease (CLD). Following administration of surfactant, preterm neonates with RDS and a birth weight of less than 1,200 g were included in this comparative observational pilot study when still mechanically ventilated and with an oxygen requirement on the third day of life. The patients (gestational age 26.1+/-0.9 weeks, birth weight 826+/-140 g, mean+/-SD) were alternately allocated to prophylactic treatment with inhaled beclomethasone (n = 7), or to early systemic dexamethasone therapy after day 10 of life, if clinically indicated (n = 9). Pulmonary inflammation and lung permeability were assessed by analyzing the levels of interleukin-8, elastase alpha1 proteinase inhibitor, free elastase activity, and albumin in tracheal aspirates on days 10 and 14 of life. The secretory component of IgA served as reference protein. We observed no significant differences in the concentrations of interleukin-8, elastase alpha1 proteinase inhibitor, and albumin between the two groups on day 10 of life. On day 14, 3 (median; range, 1-3) days following initiation of dexamethasone treatment, concentrations of the inflammatory mediators and of albumin were significantly lower in the group on systemic steroid therapy than in the group treated with inhaled steroids (P < 0.01). Additionally, there was a significant difference in oxygen requirements between both groups on day 14. In the group treated with inhaled steroids, concentrations of the inflammatory mediators, albumin, and oxygen requirements did not show a difference between day 10 and 14. We conclude that, in contrast to systemic dexamethasone treatment, a 12-day course of inhaled beclomethasone does not affect lung inflammation and pulmonary microvascular permeability in preterm infants at risk for CLD within the first 2 weeks of life.

Natural porcine surfactant (Curosurf) down-regulates mRNA of tumor necrosis factor-alpha (TNF-alpha) and TNF-alpha type II receptor in lipopolysaccharide-stimulated monocytes.

We have previously shown that Curosurf, a natural porcine surfactant, and its phospholipids effectively suppressed secretion of tumor necrosis factor (TNF-alpha) by resting and through lipopolysaccharide (LPS)-stimulated human monocytes. In this study the effect of Curosurf on monocyte mRNA for TNF-alpha and TNF-alpha type II-receptor (TNF-alpha-RII) were analyzed to evaluate the cellular mechanisms involved in the modulation of TNF-alpha expression. LPS-stimulated monocytes simultaneously exposed to Curosurf (500 microg/mL for 24 h) expressed approximately 70% less TNF-alpha mRNA when compared with control subjects (p < 0.05). In addition, 86% less TNF-alpha RII mRNA was found in monocytes exposed to Curosurf (p < 0.001). Decreased mRNA expression was clearly associated with significantly reduced secretion of TNF-alpha protein (Curosurf-exposed LPS-stimulated monocytes 3628 +/- 1873 pg/mL TNF, LPS-stimulated monocytes 31,376 +/- 2524 pg/mL TNF; mean +/- SEM, p < 0.001). The activation of the transcription factor nuclear factor-kappaB upon LPS stimulation is not affected by Curosurf incubation. This excludes that the decrease in mRNA and protein levels of TNF-alpha and TNF-alpha-RII is due to an inhibition of nuclear factor-kappaB activation by Curosurf. We conclude that Curosurf affects TNF-alpha release of LPS-stimulated monocytes at a pretranslational site by down-regulating both mRNA for TNF-alpha and TNF-alpha-RII, therefore acting as an anti-inflammatory agent within alveolar space.

Inflammatory bronchopulmonary response of preterm infants with microbial colonisation of the airways at birth.

The inflammatory indicators in the tracheobronchial aspirate (TA) of 81 ventilated preterm infants with microbial colonisation of the airways and in non-colonised neonates were analysed on the first day of life. TA was assessed for chemotactic activity, neutrophil cell count, and concentrations of leukotriene B4, C5a, interleukin-1, interleukin-8, elastase-alpha 1-proteinase inhibitor, free elastase and albumin. Concentrations of mediators were related to concentrations of the secretory component of IgA. The infants' gestational age was mean (SD) 27.9 (2.0) weeks, birthweight 945 (179) g. In 12 infants (15%) microbial colonisation of the airways was present (Ureaplasma urealyticum n = 7; bacteria n = 5). Compared with non-colonised neonates (n = 69), chemotactic activity, neutrophil count, and concentrations of interleukin-1, leukotriene B4 and elastase-alpha 1-proteinase inhibitor were significantly higher in the colonised group. The difference was most pronounced for IL-1 concentrations, both with and without correction for secretory component. There was also a trend towards increased concentrations of interleukin-8 in the latter group. There were no differences for concentrations of C5a and albumin in the TA of both groups. It is concluded that airway colonisation with U urealyticum or bacteria at birth is associated with a clinically relevant bronchopulmonary inflammatory response. Increased concentrations of interleukin-1 in TA on the first day of life may be a marker of perinatal colonisation of the airways.