Interleukin‑6 RNA knockdown ameliorates acute lung injury induced by intestinal ischemia reperfusion in rats by upregulating interleukin‑10 expression.

Abstract

Acute lung injury (ALI) is a common complication following intestinal ischemia/reperfusion (II/R) injury and contributes to the associated high mortality rate. However, the underlying mechanism is poorly understood and treatments are limited. RNA interference (RNAi) has been demonstrated to provide a promising disease treatment strategy both in vitro and in vivo. Therefore, the present study aimed to test whether blocking the proinflammatory cytokine IL-6 by RNAi may protect the lungs from remote organ injury following II/R, and to investigate the potential underlying mechanisms. A total of 176 adult healthy male Sprague-Dawley rats were randomly divided into sham, II/R, negative-control and IL-6-short hairpin (sh)RNA groups. The rats underwent II/R injury with occlusion of the superior mesenteric artery and coeliac artery to induce ischemia for 40 min, and were subsequently reperfused for 0–48 h. The negative-control group received a control lentiviral vector containing scrambled or non-specific sequences, and the IL-6-shRNA groups were administered with a vector containing an IL-6 shRNA sequence to affect RNAi-mediated knockdown of IL-6. ALI severity was determined by lung edema (lung wet/dry ratio) and histological analysis (lung injury scores). IL-6 localization, and mRNA and protein expression levels, were detected by immunofluorescence, reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. IL-10 expression induced by IL-6 knockdown in lung tissues was additionally detected. IL-6 RNAi was revealed to significantly reduce the expression of IL-6, which was associated with upregulated IL-10 expression in lung tissues. Consequently, the severities of ALI and edema induced by II/R were substantially improved. In conclusion, the present study demonstrated that IL-6 RNAi may protect the lung from ALI induced by II/R, and that this protective role may be associated with upregulation of IL-10. These findings may contribute to the development of an IL-6-RNAi-based therapeutic strategy for the treatment of II/R-induced ALI.