Dexamethasone Suppresses Expression of Nuclear Factor-kappaB in the Cells of Tracheobronchial Lavage Fluid in Premature Neonates with Respiratory Distress

Abstract

Nuclear Factor-kappaB (NF-kappaB) plays a central role in regulating the key mediators of inflammation involved in acute lung injury. The anti-inflammatory effect of steroids by suppressing pro-inflammatory cytokines may be mediated by inhibition of transcription factor NF-kappaB. The objective of this study was to determine the effect of glucocorticoid therapy on the expression of NF-kappaB in the cells of tracheobronchial lavage fluid (TBLF) in premature neonates with respiratory distress. Nineteen premature neonates requiring mechanical ventilation and receiving glucocorticoids were enrolled. Their gestational age (mean +/- SD) was 25.0 +/- 1.2 wk, birth weight 714 +/- 105 g and age of starting dexamethasone was 33 +/- 15 d. Tracheobronchial lavage fluid was collected before and 48-72 h after starting dexamethasone. NF-kappaB expression was measured by immunocytochemistry using mouse MAb against the p65 subunit of NF-kappaB on cytospin slides. The percent of cells stained and the intensity staining index were significantly higher before starting dexamethasone compared with after steroid therapy. Localization of NF-kappaB was significantly decreased in the cytoplasm and nuclei of mononuclear cells after initiation of dexamethasone therapy. The concentration of IL-8 was also significantly lower after starting dexamethasone. In conclusion, dexamethasone suppressed the expression of NF-kappaB in the cytoplasm and nuclei of mononuclear cells and decreased levels of IL-8 in TBLF from premature neonates with respiratory distress. The anti-inflammatory effects of corticosteroids may be mediated through NF-kappaB.

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

“…However, the predominant cells in TA are neutrophils and alveolar macrophages. We, and others, have shown that NF-B is localized and activated in both the neutrophils and alveolar macrophages in TA obtained from preterm infants (8,15).…”

“…We recently reported that dexamethasone therapy suppresses the activation of NF-B in pulmonary leukocytes from premature infants (8). Dexamethasone therapy not only suppressed the expression of NF-B but also decreased the concentrations of pro-inflammatory mediators in ventilated preterm infants.…”

“…Recently, we reported that dexamethasone inhibits the activation of NF-B in tracheal aspirate cells from premature ventilated infants and suppresses NF-B dependent proinflammatory mediators (8). However, the use of steroids in premature neonates has deleterious effects on brain development and is associated with developmental delay and cerebral palsy (9,10).…”

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

“…25 In addition, HMGB1 has been shown to act through NF-kB, 4,26 glucocorticoids are known to inhibit the NF-kB signaling system, 27 and Dex has been shown to suppress NF-kB expression in TA cells obtained from VPI. 28 Hence, we had expected to observe a decrease in HMGB1 levels in response to Dex treatment. This, however, did not turn out to be true.…”

Dexamethasone Therapy in Preterm Infants Developing Bronchopulmonary Dysplasia: Effect on Pulmonary Surfactant Disaturated-Phosphatidylcholine Kinetics

“…Thus, preterm infants with very severe respiratory failure are still being treated with corticosteroids, despite the awareness of the negative effects on neurodevelopment (8,27,28). The mechanisms for the improvement in lung function are not fully elucidated, and possibly include a down-regulation of lung inflammation (29) and a reduction of lung water (30,31). Scanty information exists on the role of DEXA on surfactant metabolism in general and more so in human infants.…”