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Updated: May 20, 2026
Pressure Controlled Ventilation to Induce Acute Lung Injury in Mice
Published on: May 5, 2011
Cyclin-dependent kinase inhibition reduces lung damage in a mouse model of ventilator-induced lung injury
Arie J Hoogendijk1, Maria T Kuipers, Tom van der Poll
1Center for Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam, the Netherlands. a.j.hoogendijk@amc.uva.nl
Abstract:
Mechanical ventilation (MV) has the potential to induce lung damage in healthy lungs or aggravate existing lung injury. Polymorphonuclear neutrophil (PMN) recruitment plays an important role in driving the inflammatory response in ventilator-induced lung injury (VILI). The cyclin-dependent kinase inhibitor r-roscovitine has been shown to induce apoptosis in PMNs. In this study, we investigated the potential of r-roscovitine treatment in reducing lung damage in a mouse model of VILI. Mice were tracheotomized and subjected to lung-protective MV with lower (∼7.5 mL/kg) or lung-injurious MV with higher (∼15 mL/kg) tidal volume (VT). R-roscovitine treatment enhanced apoptosis in PMNs in vitro. Ventilator-induced lung injury was associated with pulmonary PMN influx in low and high VT MV. During lung-injurious MV, r-roscovitine treatment reduced the number of PMNs and lowered levels of the lung damage markers RAGE (receptor for advanced glycation end products) and total immunoglobulin M in bronchoalveolar lavage fluid. R-roscovitine did not affect cytokine or chemokine levels in the bronchoalveolar space, neither during lung-protective nor lung-injurious MV. Thus, r-roscovitine treatment reduces lung damage in VILI, possibly dependent on increased apoptosis of PMNs.
Insights
R-roscovitine treatment reduces lung damage from mechanical ventilation. This drug promotes apoptosis in polymorphonuclear neutrophils (PMNs), decreasing lung injury markers in a VILI mouse model.
Area of Science:
- Pulmonary Medicine
- Cell Biology
- Pharmacology
Background:
- Mechanical ventilation (MV) can cause lung damage, known as ventilator-induced lung injury (VILI).
- Polymorphonuclear neutrophil (PMN) infiltration is a key factor in VILI pathogenesis.
- R-roscovitine, a cyclin-dependent kinase inhibitor, induces apoptosis in PMNs.
Purpose of the Study:
- To investigate the efficacy of r-roscovitine in mitigating lung damage in a mouse model of VILI.
- To determine if r-roscovitine's protective effects are linked to PMN apoptosis.
Main Methods:
- Mice underwent mechanical ventilation with either lung-protective or lung-injurious tidal volumes.
- R-roscovitine treatment was administered.
- PMN counts, RAGE, and IgM levels in bronchoalveolar lavage fluid were measured.
- In vitro studies assessed r-roscovitine's effect on PMN apoptosis.
Main Results:
- R-roscovitine enhanced PMN apoptosis in vitro.
- VILI was characterized by increased PMN influx.
- In lung-injurious MV, r-roscovitine reduced PMN counts and lowered RAGE and IgM levels.
- Cytokine and chemokine levels remained unaffected by r-roscovitine.
Conclusions:
- R-roscovitine treatment attenuates lung damage in a VILI mouse model.
- The protective effect of r-roscovitine may be mediated by increased PMN apoptosis.
