Anti-inflammatory effect of pre-elafin in lipopolysaccharide-induced acute lung inflammation

The aim of the present study was to evaluate the antiinflammatory activity of preelafin, an elastasespecific inhibitor, in lipopolysaccharide (LPS)induced acute lung inflammation. C57BL/6 mice were pretreated intranasally with recombinant human preelafin or vehicle only. One hour later, they were instilled intranasally with LPS (2 g/mouse). Animals were sacrificed 6 hours after LPS instillation and bronchoalveolar lavage (BAL) was performed with three 1- ml aliquots of saline. LPS induced a lung inflammation characterised by a 100-fold increase in BAL neutrophils compared to control animals (265.8+/-54.5 10(3) and 2.4+/-1.3 10(3) neutrophils/ml, respectively). Preelafin dosedependently reduced the neutrophil influx in the lung alveolar spaces by up to 84%. No elastase activity was detectable in all BAL fluids tested. Preelafin also reduced significantly LPSinduced gelatinase activity, as shown by zymography, and BAL macrophage inflammatory protein-2 (MIP-2) and KC levels, two potent neutrophil attractants and activators. Moreover, preelafin also significantly reduced mRNA levels of the three members of the IL-1 ligand family, namely IL-1alpha, IL-1beta and IL-1 receptor antagonist (IL-1Ra), type II IL-1 receptor, and TNFalpha as assessed in whole lung tissue by RNase protection assay. Thus, preelafin may be considered as a potent antiinflammatory mediator.