Background: Secretory phospholipase A2 (sPLA2) plays a pivotal role in acute respiratory distress syndrome (ARDS). This
enzyme seems an interesting target to reduce surfactant catabolism and lung tissue inflammation. Varespladib is a
specifically designed indolic sPLA2 inhibitor, which has shown promising results in animals and adults. No specific data in
pediatric ARDS patients are yet available.
Methods: We studied varespladib in broncho-alveolar lavage (BAL) fluids obtained ex vivo from pediatric ARDS patients.
Clinical data and worst gas exchange values during the ARDS course were recorded. Samples were treated with saline or
10–40–100 mM varespladib and incubated at 37uC. Total sPLA2 activity was measured by non-radioactive method. BAL
samples were subjected to western blotting to identify the main sPLA isotypes with different sensitivity to varespladib.
Results was corrected for lavage dilution using the serum-to-BAL urea ratio and for varespladib absorbance.
Results: Varespladib reduces sPLA2 activity (p,0.0001) at 10,40 and 100 mM; both sPLA2 activity reduction and its ratio to
total proteins significantly raise with increasing varespladib concentrations (p,0.001). IC50 was 80 mM. Western blotting
revealed the presence of sPLA2-IIA and –IB isotypes in BAL samples. Significant correlations exist between the sPLA2 activity
reduction/proteins ratio and PaO2 (rho = 0.63;p,0.001), PaO2/FiO2 (rho = 0.7; p,0.001), oxygenation (rho = 20.6; p,0.001)
and ventilation (rho = 20.4;p = 0.038) indexes.
Conclusions: Varespladib significantly inhibits sPLA2 in BAL of infants affected by post-neonatal ARDS. Inhibition seems to
be inversely related to the severity of gas exchange impairment
