Fms-Like tyrosine kinase-3 ligand attenuates local and systemic infection in a model of post-burn pneumonia
Background: - Burn injury induces immunosuppression and promotes infection with opportunistic pathogens. Pneumonia and sepsis are leading causes of post-burn morbidity and mortality. Fms-like tyrosine kinase-3 ligand (Flt3L) improves local and systemic resistance to P aeruginosa-associated...
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| Main Authors: | , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
June 2018
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| In: |
Shock
Year: 2018, Volume: 49, Issue: 6, Pages: 721-727 |
| ISSN: | 1540-0514 |
| DOI: | 10.1097/SHK.0000000000000964 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1097/SHK.0000000000000964 Verlag, lizenzpflichtig, Volltext: https://journals.lww.com/shockjournal/Fulltext/2018/06000/Fms_Like_Tyrosine_Kinase_3_Ligand_Attenuates_Local.15.aspx 
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| Author Notes: | Gabriel Hundeshagen, Weihua Cui, Lindsay Musgrove, Aaron Cherry, Seung-Jin Lee, Robert A. Cox, and Tracy Toliver-Kinsky |
| Summary: | Background: - Burn injury induces immunosuppression and promotes infection with opportunistic pathogens. Pneumonia and sepsis are leading causes of post-burn morbidity and mortality. Fms-like tyrosine kinase-3 ligand (Flt3L) improves local and systemic resistance to P aeruginosa-associated burn wound infection. This study evaluates the effects of post-burn prophylactic Flt3L treatment on local and systemic infection and inflammation in a murine model of pneumonia and sepsis. - Methods: - Mice received a severe scald burn, were treated with Flt3L or vehicle (CTR) for 5 days, and inoculated trans-nasally with P aeruginosa. Lung, blood, and spleen were harvested at 24 and 48 h postinoculation (p.i.) to assess infection (bacterial burden, bacteremia, distant organ manifestation) and inflammation (interleukin-6 (IL-6) and myeloperoxidase (MPO) levels). Histology correlated infection and inflammation parameters with morphology. Survival at various bacterial concentrations was monitored for 14 days p.i. - Results: - Bacterial burden was significantly reduced in lung and spleen of Flt3L-treated mice. Flt3L treatment was associated with decreased signs of pulmonary inflammation (reduced wet weight and IL-6 levels), lower incidences of bacteremia and septic distant organ manifestation, and reduced systemic inflammation (IL-6 and MPO). Histologically, reduced alveolar and peribronchiolar neutrophil and lymphocyte infiltration indicated attenuated pulmonary inflammation after Flt3L treatment. Overall survival was comparable between groups for all doses of P aeruginosa, but mortality delayed in the Flt3L-treated group. - Conclusion: - Prophylactic treatment with Flt3L could augment antimicrobial therapy of post-burn pneumonia through improvement of the initial host response to challenge with P aeruginosa, attenuate local, and systemic inflammation as well as septic pathogen dissemination. |
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| Item Description: | Gesehen am 30.04.2020 |
| Physical Description: | Online Resource |
| ISSN: | 1540-0514 |
| DOI: | 10.1097/SHK.0000000000000964 |