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Effects of interleukin‐6 (IL‐6) deletion in a murine model of ventilator‐associated lung injury (VALI)
Author(s) -
Gurkan Ozlem U,
Shin Meyeon,
He Chaoxia,
Becker Patrice M
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a10-b
Subject(s) - medicine , ards , lung , mechanical ventilation , ventilation (architecture) , shock (circulatory) , arterial catheter , anesthesia , tidal volume , pathogenesis , mean arterial pressure , circulatory system , blood pressure , respiratory system , heart rate , mechanical engineering , engineering
Rationale: IL‐6 is increased in both lung and plasma in animal models of VALI. Ventilation of ARDS patients with a low tidal volume (V T ) improved mortality, and decreased circulating levels of IL‐6. We thus hypothesized that IL‐6 might contribute to the development of VALI. Methods: To test this hypothesis, 6‐8 wk old mice deficient for IL‐6 (IL6 −/− ; n=4) or wild‐type controls (WT; n=5) were subjected to 4 hr mechanical ventilation (MV; V T 17ml/kg) following HCl aspiration. A femoral arterial catheter was placed for continuous monitoring of mean arterial pressure (MAP). After 4 hr, arterial blood gas analysis was performed, and lung injury was assessed by measurement of left lung wet/dry (W/D) weight. Results: W/D lung weight was significantly lower in IL‐6 −/− mice following MV+HCl, as compared with WT (5.3 ± 0.2 vs 6.8 ± 0.8 respectively; p<0.05). In addition, IL‐6 −/− mice were significantly protected from the development of shock as compared with WT animals (MAP 64 ± 16 vs. 18 ± 4 mmHg during last hr of MV and HCO 3 12.2 ± 2.4 vs. 5.8 ± 1.6 mmol/L respectively; p < 0.05). Conclusions: These data support an important role for IL‐6 in the pathogenesis of lung injury and circulatory collapse in this non‐septic model of VALI. Strategies to interfere with IL‐6 expression or signaling may therefore represent important therapeutic targets to limit local and systemic effects of injurious mechanical ventilation. Funded by NIH HL 073994