Role of nuclear factor-κB–interleukin-6 signaling pathway in ventilator-induced lung injury in mice

• Main Authors: Yi-An Ko, 柯怡安
• Other Authors: Ching-Mei Hsu
• Format: Others
• Language: en_US
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/53333171283886232409

碩士 === 國立中山大學 === 生物科學系研究所 === 99 === Although mechanical ventilator is a life-saving intervention, longer ventilation time and excessive tidal volume contribute to lung injury and increased incidence of infection which is associated with higher mortality. IL-6, a pleiotropic cytokine, participates in both pro- and anti-inflammatory responses. Till now, opinions of the role of IL-6 are widely divided. To study the pathogenesis mechanism of ventilator-induced lung injury (VILI), C57BL/6 mice (WT), IL-6 knockout mice (IL6-/-), chimera (IL6-/- → WT) and deletion of IκB kinase in the myeloid (IKK△mye) mice were placed on ventilator for 6 hr. WT mice were also given the IL-6-blocking antibody just before ventilation to evaluate the role of IL-6 signaling in VILI. The results revealed that the pulmonary capillary permeability, neutrophil sequestration, macrophage drifting and protein concentration in bronchoalveolar lavage fluid, and the proinflammatory cytokine levels were significantly increased in ventilated WT mice but not in those pretreated with IL-6-blocking antibody as well as IL6-/-, IKK△mye, and IL6-/- → WT chimera mice, suggesting that NF-κB–IL-6 signaling could induce inflammation which contributes to the VILI. Furthermore, the antibacterial ability of alveolar macrophages was impaired by ventilation that subsequently increased the danger of developing to ventilator-associated pneumonia.