Fms-Like tyrosine kinase-3 ligand attenuates local and systemic infection in a model of post-burn pneumonia

• Verfasst von: Hundeshagen, Gabriel [VerfasserIn]
• Verfasst von: Cui, Weihua [VerfasserIn]
• Verfasst von: Musgrove, Lindsay [VerfasserIn]
• Verfasst von: Cherry, Aaron [VerfasserIn]
• Verfasst von: Lee, Seung-Jin [VerfasserIn]
• Verfasst von: Cox, Robert A. [VerfasserIn]
• Verfasst von: Toliver-Kinsky, Tracy [VerfasserIn]
• Titel: Fms-Like tyrosine kinase-3 ligand attenuates local and systemic infection in a model of post-burn pneumonia
• Verf.angabe: Gabriel Hundeshagen, Weihua Cui, Lindsay Musgrove, Aaron Cherry, Seung-Jin Lee, Robert A. Cox, and Tracy Toliver-Kinsky
• E-Jahr: 2018
• Jahr: June 2018
• Umfang: 7 S.
• Fussnoten: Gesehen am 30.04.2020
• Titel Quelle: Enthalten in: Shock
• Ort Quelle: Hagerstown, Md. : Lippincott, Williams & Wilkins, 1994
• Jahr Quelle: 2018
• Band/Heft Quelle: 49(2018), 6, Seite 721-727
• ISSN Quelle: 1540-0514
• DOI: doi:10.1097/SHK.0000000000000964
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1696937167

Abstract

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.