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Cytokines in chronic lung disease of prematurity
1Department of Child Health, University of Leicester, UK.
Insights
Chronic lung disease of prematurity (CLD) involves increased inflammation and fibrosis in preterm infants. Key inflammatory mediators and transforming growth factor-beta1 (TGF-beta1) are elevated, suggesting complex interactions in CLD development.
Area of Science:
- Neonatal respiratory medicine
- Pulmonary pathology
- Inflammatory and fibrotic diseases
Background:
- Chronic lung disease of prematurity (CLD) is a significant respiratory condition in preterm infants.
- Autopsies reveal increased fibroblast proliferation, collagen, and fibronectin in lungs of infants with CLD.
- Persistence of neutrophils in broncho-alveolar fluid is linked to CLD development.
Purpose of the Study:
- To investigate the role of inflammatory mediators and fibrotic factors in the pathogenesis of CLD.
- To identify specific cytokines and cellular sources involved in CLD.
- To explore the temporal relationship between inflammation and fibrosis in CLD.
Main Methods:
- Analysis of broncho-alveolar lavage fluid from preterm infants with and without CLD.
- Measurement of pro-inflammatory cytokines (IL-1 beta, IL-6, IL-8) and neutrophil mediators (soluble intercellular adhesion molecule, neutrophil elastase).
- Reverse transcriptase-polymerase chain reaction (RT-PCR) to determine mRNA sources of cytokines.
- Assessment of pro-fibrotic cytokine transforming growth factor-beta1 (TGF-beta1) and collagen in lavage fluid and lung tissue.
Main Results:
- Elevated levels of IL-1 beta, IL-6, IL-8, soluble intercellular adhesion molecule, and neutrophil elastase in infants who developed CLD.
- Luminal cells identified as potential sources of IL-6, while non-luminal cells may produce IL-1 beta and IL-8.
- Increased active and total TGF-beta1 in lavage fluid, with elevated type I procollagen and TGF-beta in lung tissue.
- Inflammatory mediator increases peaked at 10 days, while TGF-beta1 increase was maximal at 4 days of age.
Conclusions:
- The development of CLD involves a complex interplay between inflammation and fibrosis.
- Specific inflammatory mediators and TGF-beta1 play crucial roles in CLD pathogenesis.
- Prenatal factors may significantly contribute to the development of CLD in preterm infants.
Abstract:
Chronic lung disease of prematurity (CLD) is a common respiratory disorder of preterm infants. At autopsy, fibroblast proliferation, and components of the extracellular matrix, including collagen and fibronectin, are markedly increased in the lungs of infants who die from CLD. Examination of broncho-alveolar fluid suggests that the persistence of neutrophils is associated with the development of CLD. In our studies, the pro-inflammatory cytokines, interleukin-1 beta (IL-1 beta) and interleukin-6, (IL-6) and mediators which reflect neutrophil recruitment and activation, including soluble intercellular adhesion molecule, interleukin-8 (IL-8) and neutrophil elastase, were increased in lavage fluid obtained from infants who developed CLD when compared to infants who did not. Furthermore, semiquantitative reverse transcriptase-polymerase chain reaction of mRNA extracted from lavage cells suggested that luminal cells may be the source of IL-6 detected in lavage fluid but non-luminal cells may be the sources of IL-1 beta and IL-8. Fibrosis is thought to be mediated by the pro-fibrotic cytokines including transforming growth factor-beta1 (TGF-beta 1). Both active and total TGF-beta 1 were increased in lavage fluid from infants who developed CLD. Furthermore, both type I procollagen and TGF-beta were increased qualitatively in lung tissue obtained at autopsy from infants who died from respiratory failure. The increase in inflammatory mediators was maximal at 10 days of age. By contrast, the increase in TGF-beta 1 was maximal at 4 days of age. This suggests that the interaction between inflammation and fibrosis in CLD is complex, and that prenatal factors may be important in the pathogenesis of CLD.