» Articles » PMID: 18996903

Mechanical Ventilation Enhances Lung Inflammation and Caspase Activity in a Model of Mouse Pneumovirus Infection

Abstract

Severe infection with respiratory syncytial virus (RSV) in children can progress to respiratory distress and acute lung injury (ALI). Accumulating evidence suggests that mechanical ventilation (MV) is an important cofactor in the development of ALI by modulating the host immune responses to bacteria. This study investigates whether MV enhances the host response to pneumonia virus of mice (PVM), a mouse pneumovirus that has been used as a model for RSV infection in humans. BALB/c mice were inoculated intranasally with diluted clarified lung homogenates from mice infected with PVM strain J3666 or uninfected controls. Four days after inoculation, the mice were subjected to 4 h of MV (tidal volume, 10 ml/kg) or allowed to breathe spontaneously. When compared with that of mice inoculated with PVM only, the administration of MV to PVM-infected mice resulted in increased bronchoalveolar lavage fluid concentrations of the cytokines macrophage inflammatory protein (MIP)-2, MIP-1alpha (CCL3), and IL-6; increased alveolar-capillary permeability to high molecular weight proteins; and increased caspase-3 activity in lung homogenates. We conclude that MV enhances the activation of inflammatory and caspase cell death pathways in response to pneumovirus infection. We speculate that MV potentially contributes to the development of lung injury in patients with RSV infection.

Citing Articles

Long-Term Pulmonary Dysfunction by Hyperoxia Exposure during Severe Viral Lower Respiratory Tract Infection in Mice.

Lilien T, Gunjak M, Myti D, Casado F, van Woensel J, Morty R Pathogens. 2022; 11(11).

PMID: 36422586 PMC: 9696792. DOI: 10.3390/pathogens11111334.


Mechanical Ventilation Exacerbates Poly (I:C) Induced Acute Lung Injury: Central Role for Caspase-11 and Gut-Lung Axis.

Jin S, Ding X, Yang C, Li W, Deng M, Liao H Front Immunol. 2021; 12:693874.

PMID: 34349759 PMC: 8327178. DOI: 10.3389/fimmu.2021.693874.


Persistent Airway Hyperresponsiveness Following Recovery from Infection with Pneumonia Virus of Mice.

Limkar A, Percopo C, Redes J, Druey K, Rosenberg H Viruses. 2021; 13(5).

PMID: 33922096 PMC: 8143513. DOI: 10.3390/v13050728.


Pneumovirus-Induced Lung Disease in Mice Is Independent of Neutrophil-Driven Inflammation.

Cortjens B, Lutter R, Boon L, Bem R, van Woensel J PLoS One. 2016; 11(12):e0168779.

PMID: 28005954 PMC: 5179008. DOI: 10.1371/journal.pone.0168779.


Application of fiberoptic bronchscopy in patients with acute exacerbations of chronic obstructive pulmonary disease during sequential weaning of invasive-noninvasive mechanical ventilation.

Song R, Qiu Y, Chen Y, Ji Y World J Emerg Med. 2014; 3(1):29-34.

PMID: 25215035 PMC: 4129828. DOI: 10.5847/wjem.j.issn.1920-8642.2012.01.005.


References
1.
ODonnell D, Milligan L, Stark J . Induction of CD95 (Fas) and apoptosis in respiratory epithelial cell cultures following respiratory syncytial virus infection. Virology. 1999; 257(1):198-207. DOI: 10.1006/viro.1999.9650. View

2.
Sheeran P, Jafri H, Carubelli C, Saavedra J, JOHNSON C, Krisher K . Elevated cytokine concentrations in the nasopharyngeal and tracheal secretions of children with respiratory syncytial virus disease. Pediatr Infect Dis J. 1999; 18(2):115-22. DOI: 10.1097/00006454-199902000-00007. View

3.
Vlahakis N, Schroeder M, Limper A, Hubmayr R . Stretch induces cytokine release by alveolar epithelial cells in vitro. Am J Physiol. 1999; 277(1):L167-73. DOI: 10.1152/ajplung.1999.277.1.L167. View

4.
Matute-Bello G, Liles W, Steinberg K, Kiener P, Mongovin S, Chi E . Soluble Fas ligand induces epithelial cell apoptosis in humans with acute lung injury (ARDS). J Immunol. 1999; 163(4):2217-25. View

5.
Domachowske J, Bonville C, Rosenberg H . Animal models for studying respiratory syncytial virus infection and its long term effects on lung function. Pediatr Infect Dis J. 2004; 23(11 Suppl):S228-34. DOI: 10.1097/01.inf.0000144672.81955.a4. View