Effects of sivelestat treatment on acute lung injury in paraquat-intoxicated rats.

Lung injury is the main cause of death in acute paraquat (PQ) intoxication. Sivelestat (SV), a neutrophil elastase inhibitor, is effective in reducing inflammation in acute lung injury. The aim of this study was to examine the effect of SV on acute lung injury in PQ-intoxicated rats. Seven-week-old male Sprague-Dawley rats were randomly assigned to four groups: (1) control group (group N; n = 5); (2) PQ + normal saline (group P; n = 6); (3) normal saline + SV (group S; n = 6) and (4) PQ + SV (group PS; n = 6). SV treatment (intraperitoneally [i.p.], 20 mg/kg) was performed 30 minutes after PQ injection (i.p., 100 mg/kg), and injections were continued every hour for a total of five doses. One hour after the last treatment, blood samples were obtained for analysis of interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α). Lung sections were stained with hematoxylin--eosin for light microscopic analysis. Neutrophil infiltration score of group PS was significantly lower than that of group P (p < 0.05). But, other scores and total score had no significant differences. IL-6 of group PS did not differ, compared to group P. In addition, there were no differences among the four groups. TNF-α of group PS was reduced, in comparison to the level of group P. SV attenuated neutrophil infiltration in PQ-induced acute lung injury in rats. In addition, systemic inflammation was partially suppressed with SV treatment, suppressing TNF-α production. These results suggest that SV reduces paraquat-induced lung injury, at least partially, by inhibiting neutrophil infiltration and TNF-α secretion.