Recombinant human thioredoxin-1 becomes oxidized in circulation and suppresses bleomycin-induced neutrophil recruitment in the rat airway

Thioredoxin-1 (TRX) is a redox-active protein with anti-inflammatory effects. This study investigated the optimal delivery method and the mechanisms of recombinant human TRX (rhTRX) to suppress neutrophil recruitment in a rat bleomycin (BLM)-induced sustained acute lung injury model. In male Wister rats intratracheally administered with 0.125 mg/kg BLM, 8 mg/kg/day rhTRX was intravenously administered on days 3-6 using one of three protocols: daily bolus injection, 3 h daily infusion or continuous infusion for 96 h. Only the continuous-infusion of rhTRX significantly reduced the neutrophil infiltration compared with the other two methods. The BLM-induced down-regulation of L-selectin expression on circulating neutrophils was inhibited by rhTRX. Oxidized rhTRX showed a comparable effect with reduced rhTRX and rhTRX incubated with plasma or circulating in plasma was more than 99% oxidized. These results suggest that rhTRX becomes oxidized in circulation and continuous infusion of rhTRX suppresses neutrophil recruitment in the airway.