NF- B in tracheal lavage fluid from intubated premature infants: association with inflammation, oxygen, and outcome

Abstract

Objectives: To determine if tracheal lavage concentrations of the transcription factor NF-kB, which is activated by risk factors associated with bronchopulmonary dysplasia (BPD) and induces expression of cytokines associated with BPD, is related to BPD in premature infants. Design: Serial tracheal lavage samples from intubated premature infants were analysed for cell count and concentrations of interleukin (IL)8 and NF-kB, corrected for dilution by secretory component concentrations. Setting: Level III university hospital neonatal intensive care unit. Patients: Thirty three intubated infants (mean (SD) birth weight 903 (258) g, median gestation 27 weeks (range 24-31)) in the first 14 days of life. Main outcome measures: Tracheal effluent NF-kB, IL8, and cell counts, corrected for dilution by secretory component measurement. Results: Square root transformed NF-kB concentrations were significantly related to signs of inflammation (cell count, p = 0.002; IL8, p = 0.019) and to simultaneous fraction of inspired oxygen in samples from the first 3 days of life (r = 0.512, p,0.003). Of the 32 subjects with samples in the first 3 days of life, the half who either died or had BPD had higher NF-kB concentrations than those without BPD (square root concentration 0.097 (0.043) v 0.062 (0.036) mg/mg protein/mg secretory component, p = 0.018). Conclusions: Tracheobronchial lavage NF-kB concentrations are related to lung inflammation, oxygen exposure, and pulmonary outcome in intubated preterm infants. NF-kB activation may be an early critical step leading to BPD. B ronchopulmonary dysplasia (BPD) occurs primarily in premature infants who are mechanically ventilated and exposed to oxygen early in their life. It is associated with early inflammation of the airways and lung interstitium, ), which are raised in tracheobronchial lavage obtained from patients who progressed to BPD. Expression of these mediators is partially controlled through the activation of transcription factors. These are proteins that, on appropriate stimulation, attach to a recognition sequence in the promoter region of specific genes.6 One of these transcription factors is nuclear factorkappa B (NF-kB).NF-kB, a ubiquitous transcription factor, promotes the expression of many genes, including proinflammatory cytokines associated with the development of BPD. It is activated by a variety of factors, including infectious stimuli, inflammatory cytokines, deformation, oxidants, and other causes of cell stress.7 8 It has roles in controlling apoptosis and cell proliferation and differentiation 9 and may be involved in lung development. 10Activation of NF-kB occurs in many inflammatory conditions both in vivo and in vitro. Lung macrophages from adults at risk of acute respiratory distress syndrome had significantly more activated NF-kB than from those who did not develop acute respiratory distress syndrome.11 NF-kB activation was higher in monocytes and neutrophils in adults with fatal systemic inflammatory response than in those who survived. 12As NF-kB is activate...

Hyperoxia-induced NF-κB activation occurs via a maturationally sensitive atypical pathway

“…Multiple models have shown increased NF-B activation in neonates compared with adults after exposure to inflammatory and oxidant stimuli (39,64,68). In preterm infants, increased NF-B activation has been linked to respiratory distress syndrome and an increased risk of developing BPD (10,18,20). However, whether this increased activation is a protective response to multiple inflammatory and oxidant stimuli or whether it represents a dysregulated reaction to stress remains unexplored (3,29,30,42).…”

Azithromycin Suppresses Activation of Nuclear Factor-kappa B and Synthesis of Pro-inflammatory Cytokines in Tracheal Aspirate Cells From Premature Infants

“…NF-B is also expressed in alveolar macrophages of mechanically ventilated preterm neonates (6). Recently, a study has shown that the activation of NF-B is increased in tracheal aspirates (TA) cells of preterm infants who developed bronchopulmonary (BPD) (7). Thus, it appears that the activation of NF-B is central to the development of pulmonary inflammation and lung injury.…”

High-mobility group box-1 protein in tracheal aspirates from premature infants: relationship with bronchopulmonary dysplasia and steroid therapy

“…4,5 HMGB1 has also been shown to activate nuclear factor-kappa B (NF-kB). 4 Earlier reports have suggested the involvement of NF-kB in BPD, 8,9 and necrotic cell death is an important consequence of hyperoxia-induced lung injury, 10 in addition to sepsis 5 and ventilator-induced lung injury. 11 The role of HMGB1 in neonatal lung injury and the development of BPD in premature infants are not known.…”