1496 forms [35]. Both fractions of meconium, water-soluble (containing bilirubin, bile acids, enzymes, etc.) and lipid- soluble (containing free fatty acids, cholesterol, triglycerides, etc.) ones, impair lung functions [56]; however, the lipid- soluble fraction is much more deleterious [76]. The dysfunction of surfactant is further potentiated by plasma proteins leaking through an injured alveolocapillary mem- brane, as well as by the action of proteolytic enzymes and reactive oxygen and nitrogen species (RONS) released from activated cells during the inflammation. Meconium itself acts as a potent chemoattractant for neutrophils [87], increasing their number in the lungs within several hours after the aspiration, which is linked with their decrease in the blood [55, 66]. In addition, meconium is a source of pro-inflammatory mediators, such as interleukins (IL) -1, -6 and -8, tumour necrosis factor α (TNFα), etc. [20]; thus, it may induce inflammation directly or indirectly through the stimulation of oxidative burst in neutrophils [69] and alveolar macrophages [17]. The activated macrophages and released cytokines may stimulate the adhesion of neutrophils on the endothelium and the formation of micro- emboli in the capillary bed, participating in the onset of pulmonary hypertension. This process is facilitated by complement, the activation of which has been proved also in MAS [11]. The activated cells (leukocytes, platelets, epithelial and endothelial cells, etc.) produce a wide spectrum of substances like TNFα, IL, leukotrienes (LT), prostaglandins (PG), platelet-activating factor (PAF), proteolytic enzymes and RONS, injuring the lung parenchyma and surfactant [27, 92]. Inflammatory cytokines induce angiotensin II (ANG II) expression which, after binding to AT1 receptors, cause apoptotic death of the lung cells as well [82]. Subsequently, a leak of proteinaceous fluid and cells into the alveolar spaces through the alveolocapillary membrane further deteriorates the lung function. In addition, meconium contains high concen- trations of phospholipase A2 (PLA2), which may directly or via the arachidonic acid metabolism increase the production of lipid mediators and participate in the apoptosis of epithelial cells [29] and surfactant dysfunction [65]. Meconium also enhances the expression of inducible cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in the macrophages and epithelial and endothelial cells [42, 44]. Furthermore, the release of bronchoactive substances like LT and PAF is probably responsible for increased airway reactivity to bronchoconstrictor agents [38, 55]. Meconium aspiration is often associated with pulmonary vasoconstriction from hypoxia and/or from the vasocon- striction effect of meconium and substances released during the inflammation. The presence of meconium in the amniotic fluid may cause ischemic changes of the lungs, umbilical cord and placenta [7]. Postnatal meconium instillation elevates the pulmonary artery pressure and vascular resistance in a concentration-dependent manner Eur J Pediatr (2011) 170:1495–1505 [28], which is linked with higher levels of thromboxane A2 (TXA2), LT, PG and endothelin-1 (ET-1) [41, 68, 86]. Glucocorticoids Mechanisms of action Cortisol, a major endogenous glucocorticoid (GC), is secreted by the cortex of adrenal glands. Only a small proportion of GCs (<10%) is free and metabolically active since majority of GCs is bound to proteins during their transport in the blood. The daily production of cortisol in adults may be about 13– 20 mg and may increase up to 300 mg/day [75]. In children and adolescents, the daily production of cortisol is about 6.8 mg/m2/day [45]. The plasma concentration of cortisol in adults varies in the range of 50–500 nmol/l, in the term newborns about 140 nmol/l and in premature newborns about 180 nmol/l [75]. The action of GCs contributes to the compensatory mechanisms which help the body to get a stress situation under control. GCs supply energy for these processes by protein catabolism, gluconeogenesis and gluco- genesis, finally resulting in hyperglycaemia, hyperlipidemia and other changes in the blood, bones, muscles and cardiovascular, gastrointestinal, endocrinal and central ner- vous systems [24, 34]. Free GC molecules penetrate through the cell membrane into the cytoplasm, where they interact with a specific glucocorticoid receptor (GR). Heat-shock protein HSP90, which is normally attached to a free GR and prevents its transport to the nucleus, is released in this process. After binding GCs to a GR receptor, the activated complex moves into the nucleus and binds to a specific nuclear sequence of DNA (glucocorticoid-responsive element, GRE). As a result, it may activate or inhibit the transcription of mRNA and thereby modulate the production of various proteins (Figs. 1 and 2). The newly synthesized substances then mediate physiological or pharmacological responses, including met- abolic and anti-inflammatory effects. In case of their anti-inflammatory action, the activated GR complex interacts with negative-responsive element (GRE−). The subsequent inhibition of transcription factors including nuclear factor (NF)-κB and protein activator (AP)-1 inhibits the expression of pro-inflammatory cyto- kines (IL-1, IL-6, IL-8, TNFα, etc.), enzymes (PLA2, COX-2, iNOS, etc.) and other biologically active substan- ces such as PAF, ET-1, ICAM-1, etc. [24, 34, 57] (Fig. 2). The anti-inflammatory effect of GCs is supplied also through enhancing the activity of lipocortines. The in- creased transcription of lipocortine-1 in leukocytes is related to the interaction of GC–GR complex to the positive-responsive element of DNA (GRE+). Lipocortines inhibit the activity of PLA2 and thereby decrease the