Increased Activity of Interleukin-6 but not Tumor Necrosis Factor-α in Lung Lavage of Premature Infants is Associated with the Development of Bronchopulmonaiy Dysplasia

Abstract

Although considerable evidence suggests that bronchopulmonary dysplasia (BPD) is the result of prolonged inflammation and impaired healing of the immature lung, the mediators that regulate inflammation in neonatal lung injury have not been completely elucidated. We examined whether the cytokines IL-6 and tumor necrosis factor-a (TNF) interact to modulate a cascade of cell-cell signaling events involved in inflammation contributing to the development of BPD. To determine the relative activities of these cytokines in neonatal lung injury, lung lavage samples were serially obtained from 1 to 28 d from 11 infants with self-limited respiratory distress syndrome (RDS), 19 infants with evolving BPD, and 10 control infants ventilated for nonpulmonary reasons. On the first day of life, there were no differences in antigenic IL-6 concentrations in lavage fluids among the BPD, RDS, and control groups, but IL-6 activity determined by the 7TD1 proliferation assay was 15-fold and 6.6-fold higher in lung lavage of infants who developed BPD compared with activities in lavage from control and RDS infants, respectively (control, Exogenous surfactant therapy has dramatically improved survival of very-low-birth-weight infants with RDS, but it has not affected the incidence of the neonatal chronic lung disorder B P D (1). This suggests that factors in addition t o surfactant deficiency contribute t o neonatal lung injury. Pathologic findings in B P D are consistent with a process of prolonged lung inflammation and impaired healing (2, 3). In human infants with RDS (4-6) 49.4 ? 17.6; RDS, 117.3 2 59.6; BPD, 779.5 2 212.6 x 10' hybridoma units/L, mean * SEM,p = 0.02). This suggests that pathways for inactivating or inhibiting IL-6 that may be present in the lungs of RDS and control infants may be deficient in BPD infants. IL-6 activity remained elevated in lavage of BPD infants for the first 2 wk and declined to low levels by d 28. There were no differences among groups on the first day of life for TNF antigen concentration or TNF activity determined by the L929 bioassay. Detectable but low TNF activity was found in BPD samples, with peak activity found in d-14 samples. Differences in complex interactions among these and other cytokines with their receptors and inhibitors may predispose some infants with RDS to develop BPD. (Pediuh. Res 36: 244-252, 1994) Abbreviations RDS, respiratory distress syndrome BPD, bronchopulmonary dysplasia TNF, tumor necrosis factor-a PROM, prolonged rupture of membranes and in primate models of acute lung injury (7), there is a rapid influx of neutrophils into the lung during the first 48 t o 96 h after initial injury followed b y a n increase in alveolar macrophages with subsequent resolution of airw a y inflammation. In contrast, in infants w h o develop BPD, the neutrophil influx is prolonged and the alveolar macrophage entry is delayed and blunted (5). nolysis (13), the mediators that regulate neonatal lung

Interleukin (IL)-1β in Tracheal Aspirates from Premature Infants Induces Airway Epithelial Cell IL-8 Expression via an NF-κB Dependent Pathway

“…During the first days of postnatal life, an influx of polymorphonuclear leukocytes and macrophages is seen in the tracheal aspirates of mechanically ventilated premature infants who later develop BPD (1). Elevations of pro-inflammatory cytokines such as IL-8, IL-6, IL-1␤, and TNF-␣ are also seen (2)(3)(4)(5)(6)(7). Similar findings are present in animal models of BPD (8) and hyperoxic exposure (9).…”

Pulmonary Ureaplasma urealyticum Is Associated with the Development of Acute Lung Inflammation and Chronic Lung Disease in Preterm Infants

“…These findings have been confirmed by many others (10,11), and it is now generally accepted that pulmonary inflammation is a risk factor for the development of CLD (12). The exact injurious factors that trigger and maintain the inflammatory response remain elusive.…”

Bronchoalveolar lavage in children. ERS Task Force on bronchoalveolar lavage in children. European Respiratory Society

“…It is unknown whether repeated insertion of the catheter samples the same area. Although most investigators use normal saline, at either room temperature or warmed to 378C, the volume instilled is either based on weight [21,114] or is fixed empirically [118]. The number of aliquots is usually one or two with the first aliquot probably reflecting bronchial milieu and the second more bronchoalveolar regions [114].…”