Mechanical Ventilation Induces a Toll/Interleukin-1 Receptor Domain-containing Adapter-inducing Interferon beta-dependent Inflammatory Response in Healthy Mice

作者：Vaneker Michiel^*; Heunks Leo M A; Joosten Leo A; van Hees Hieronymus W H; Snijdelaar Dirk G; Halbertsma Feico J; van Egmond Jan; Netea Mihai G; van der Hoeven Johannes G; Scheffer Gert Jan

来源：Anesthesiology, 2009, 111(4): 836-843.

DOI：10.1097/aln.0b013e3181b76499

Background: Mechanical ventilation (MV) can induce lung injury. Proinflammatory cytokines have been shown to play an important role in the development of ventilator-Induced lung injury. Previously, the authors have shown a role for Toll-like receptor 4 signaling. The current study aims to investigate the role of Toll/interleukin-1 receptor domain-containing adapter-inducing interferon-beta (TRIF), a protein downstream of Toll-like receptors, in the development of the inflammatory response after MV in healthy mice.
Methods. Wild-type C57BL6 and TRIF mutant mice were mechanically ventilated for 4 h. Lung tissue and plasma was used to investigate changes in cytokine profile, leukocyte influx, and nuclear factor-kappa B activity. In addition, experiments were performed to assess the role of TRIF in changes in cardiopulmonary physiology after MV.
Results: MV significantly Increased messenger RNA expression of interleukin (IL)-1 beta in wild-type mice, but not in TRIF mutant mice. In lung homogenates, MV Increased levels of IL-1 alpha, IL-1 beta, and keratinocyte-derived chemokine in wild-type mice. In contrast, in TRIF mutant mice, only a minor Increase in IL-1 beta and keratinocyte-derived chemokine was found after MV. Nuclear factor-kappa beta activity after MV was significantly lower in TRIF mutant mice compared with wild-type mice. In plasma, MV increased levels of IL-6 and keratinocyte-derived chemokine. In TRIF mutant mice, no increase of IL-6 was found after MV, and the increase in keratinocyte-derived chemokine appeared less pronounced. TRIF deletion did not affect cardiopulmonary physiology after MV.
Conclusions. The current study supports a prominent role for TRIF in the development of the pulmonary and systemic inflammatory response after MV.

• 出版日期2009-10