Abstract
Introduction: Persistent neutrophil-dominated lung inflammation is strongly implicated in the development of Chronic Lung Disease of Prematurity (CLD). The complex of interleukin-6 (IL-6) and its soluble receptor, sIL-6R, can activate trans-signalling in cells lacking the cell-surface receptor IL-6R; a soluble form of the signal-transducer gp130 can inhibit trans-signalling by specifically binding to the sIL-6R/IL-6 complex. As anti-inflammatory effects of IL-6 trans-signalling can shape resolution of inflammatory responses, we studied the expression, inter-relationships and functional activity of IL-6, sIL-6R and sgp130 in the preterm lung.
Methods: Cytokines were measured by ELISA in bronchoalveolar lavage fluid (BALF) from ventilated preterm infants born at ≤32 weeks gestational age. Functional activity was determined in a sensitive, IL-6 specific bioassay using mouse B9 cells. Results were compared between the CLD group (persistent inflammation) and non-CLD group (resolved).
Results: Inflammatory cells and chemokines, CXCL8 and CCL2, were higher in the CLD group (p<0.05). IL-6 and sIL-6R were comparable between the two groups; however, peak sgp130 was higher in the CLD group (CLD 65.3 ng/ml vs non CLD 20.8 ng/ml p=0.01), as was the anti trans-signalling ratio of sgp130/sIL-6R (p=0.02). Functional activity of IL-6 in the bioassay was similar between the two groups. Trans-signalling activity was not noted in any of the samples in the bioassay.
Conclusions: Increased sgp130 in the lungs of preterm infants may be responsible for impaired trans-signalling by the sIL-6R/IL-6 complex. Better understanding of this pathway may lead to therapies to resolve lung inflammation in preterm infants.
- © 2011 ERS
