Format

Send to

Choose Destination
J Trauma Acute Care Surg. 2017 Apr;82(4):758-765. doi: 10.1097/TA.0000000000001389.

Valproic acid mitigates the inflammatory response and prevents acute respiratory distress syndrome in a murine model of Escherichia coli pneumonia at the expense of bacterial clearance.

Author information

1
From the Department of Surgery (G.K., M.G., E.K., B.S., A.S., P.A.B.), Departments of Medicine, Microbiology and Biochemistry, Pulmonary Center (J.P.M.), and Department of Pathology and Laboratory Medicine (D.R.), Boston University School of Medicine, Boston, Massachusetts.

Abstract

BACKGROUND:

Histone deacetylase inhibitors (HDACI) are members of a family of epigenetic modifying agents with broad anti-inflammatory properties. These anti-inflammatory properties may have important therapeutic implications in acute respiratory distress syndrome (ARDS). However, administration of HDACI may create an immunosuppressive environment conducive to bacterial growth. Accordingly, the aim of the current study is to investigate the effect of HDACI valproic acid (VPA) on host inflammatory response and bacterial burden in a murine model of Escherichia coli pneumonia-induced ARDS.

METHODS:

ARDS was induced in male C57BL6 mice (n = 24) by endotracheal instillation of 3 × 10 E. coli. VPA (250 mg/kg) was administered 30 minutes after E. coli instillation in the intervention group. Blood samples were collected at 3 and 6 hours, and animals were sacrificed at 6 hours. Bronchoalveolar lavage (BAL) was performed, and tissue specimens were harvested. Cytokine levels were measured in blood and BAL, and so was transalveolar protein transit. Cell counts and colony forming units were quantified in BAL fluid.

RESULTS:

VPA reduced neutrophil influx into the lungs and local tissue destruction through decreased myeloperoxidase activity. It also ameliorated the pulmonary and systemic inflammatory response. This led to greater bacterial proliferation in the pulmonary parenchyma.

CONCLUSION:

Administration of VPA in a clinically relevant bacterial model of murine ARDS mitigates the host inflammatory response, essentially preventing ARDS, but creates an immunosuppressive environment that favors bacterial overgrowth.

PMID:
28099388
PMCID:
PMC5360476
DOI:
10.1097/TA.0000000000001389
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wolters Kluwer Icon for PubMed Central
Loading ...
Support Center