Inflammatory mechanisms in neonatal chronic lung disease

Chronic lung disease (CLD) of preterm infants has a multifactorial aetiolog y. Oxygen toxicity, mechanical injury (barotrauma), volutrauma as well as p renatal and postnatal infections most likely contribute to pulmonary injury in the immature lung of preterm infants. There is sufficient evidence that respiratory distress syndrome and CLD are associated with a significant in flammatory response of the airways and the interstitium of the lungs, besid es neutrophils, alveolar and interstitial macrophages immunoreactive for tu mour necrosis factor-alpha (TNF-alpha) are found in large numbers. Phagocyt e influx is possibly mediated by chemotactic and chemokinetic factors prese nt in the bronchoalveolar secretions: interleukin-8, leukotriene B-4, C5a, elastin fragments, macrophage-inflammatory protein-1 alpha and other chemok ines. Increased concentrations of soluble selectins and intercellular adhes ion molecule-1 in broncho-alveolar secretions and the serum of infants with CLD possibly reflect neutrophil diapedesis. Lipid mediators including leuk otrienes, prostacyclin, platelet activating and other mediators such as the pro-inflammatory cytokines TNF-alpha, interleukin-1 and -6, exert various effects on the airways and the vascular system by increasing the microvascu lar permeability which is one of the most important pathophysiological fact ors of early CLD. Pulmonary cells of preterm infants may be unable to downr egulate inflammation through the expression of the anti-inflammatory cytoki ne interleukin-10. Inflammatory cells can cause severe lung damage by relea se of potent proteases (elastase), cytokines and by generation of toxic oxy gen radicals (O-2-, (OH)-O-.). The presence of free elastase acitivity and the protease-antiprotease imbalance has been well documented. In fact, incr eased concentrations of products of elastolytic fibre degradation and of ox ygen radical mediated lipid peroxidation were detected in infants with CLD. Conclusion The complex interaction between mediators of inflammation and fi brosis has still to be defined. Moreover, the possible interference of infl ammation with postnatal lung development especially with the alveolarizatio n process has not been evaluated yet.