Inflammatory Response and Apoptosis in Newborn Lungs after Meconium Aspiration

Abstract

An important feature of meconium-instilled newborn lungs is an inflammatory response and apoptotic cell death. It was recently demonstrated by our group and supported by several other investigators in a relatively short period of time. Apoptosis exists also in healthy lungs, but in meconium-instilled lungs its level is usually dramatically higher. Apoptosis is characterized by loss of cell function, decrease in cell size, and its morphology. Apoptosis plays an important role in normal cell life, but increased levels of apoptosis induce great damage for any tissues. Apoptosis in the lungs has been greatly overlooked for the past decade, and meconium-induced apoptosis is a relatively new event and not effectively studied at the present time. This Review summarized current knowledge regarding meconium-induced inflammation and apoptosis in newborn lungs.

Serum Cytokine and Chemokine Profiles in Neonates With Meconium Aspiration Syndrome

“…30,31 However, in MAS, the relationships between induction of cytokines and chemokines and pathophysiology are poorly understood, although levels of a few cytokines in sera of MAS patients have been investigated. 4 The assessment of various cytokines and chemokines levels is, therefore, important to precisely understand the mechanisms of lung injuries in MAS. IL-4, IL-10, and IL-13 act as anti-inflammatory cytokines and prevent abnormal inflammatory reactions in vivo.…”

“…4,10,38,40 For example, de Beaufort et al 10 showed that the addition of meconium induces the production of IL-8 from A549 epithelial cells, and Zagariya et al 24 demonstrated that mRNA for TNF-␣, IL-6, and IL-8 is expressed in A549 epithelial cells stimulated by meconium. These results suggest that meconium itself is inducible for severe inflammatory responses.…”

“…1 The major pathogenesis of chemical pneumonitis in MAS may be responsible for the transmigration and infiltration of inflammatory cells, including neutrophils and macrophages found in the alveoli, larger airways, and the lung parenchyma, as well as bacterial pneumonia. [1][2][3][4] Moreover, Castellheim et al 5 reported that meconium aspiration can lead to progressive systemic inflammatory responses syndrome in newborn piglets, involving granulocyte activation and interleukin (IL)-6 and IL-8 release. Thus, severe MAS can be life threatening because of multiple organ failure with devastating inflammation.…”

“…Thus, severe MAS can be life threatening because of multiple organ failure with devastating inflammation. 4,6 Previous reports demonstrated that cytokines and chemokines as immunologic responders may be strongly linked to the various infectious lung diseases. 7,8 Although MAS is not principally an infectious disease, its pathophysiology is similar in terms of the process of inflammatory response to pneumonia caused by various pathogens.…”

Human Meconium Has a Pulmonary Vascular and Airway Smooth Muscle Relaxant Effect

“…Last, lung instillation of meconium has been shown in animal models to induce airway epithelial cell and pneumocyte apoptosis via a mechanism that involves the reninangiotensin pathway and angiotensin II production (23)(24)(25)(26). Angiotensin type 1 receptors appear to predominate in the adult rat lung and modulate the chronic hypoxia induced pulmonary hypertension (27).…”