Therapy with anti-flagellin A monoclonal antibody limits Pseudomonas aeruginosa invasiveness in a mouse burn wound sepsis model

• Published in: Burns 2009-05, Vol.35 (3), p.390-396
• Main Authors: Barnea, Yoav, Carmeli, Yehuda, Neville, Lewis F, Kahel-Reifer, Hamutal, Eren, Rachel, Dagan, Shlomo, Navon-Venezia, Shiri
• Format: Article
• Language: English
• Subjects: Animals; Anti-flagellin A; Antibodies, Monoclonal - therapeutic use; Antibody Specificity; Bacterial diseases; Bacterial sepsis; Biological and medical sciences; Burns; Burns - drug therapy; Burns - microbiology; Critical Care; Female; Flagellin - immunology; Human bacterial diseases; Immunohistochemistry; Infectious diseases; Medical sciences; Mice; Mice, Inbred C57BL; Mouse burn wound sepsis model; Pseudomonas aeruginosa; Pseudomonas aeruginosa - immunology; Pseudomonas Infections - drug therapy; Pseudomonas Infections - immunology; Sepsis - drug therapy; Sepsis - microbiology; Skin - pathology; Traumas. Diseases due to physical agents; Wound Infection - microbiology
• ISSN: 0305-4179; 1879-1409
• DOI: 10.1016/j.burns.2008.08.014

Abstract Background The aim of this study was to evaluate the effect of an anti-flagellin sub-type monoclonal antibody (anti-fla-a) on Pseudomonas aeruginosa infection in a mouse burn model and to assay bacterial dissemination and invasiveness. Methods After immediate post-burn infection with P. aeruginosa , mortality and morbidity (daily weight changes) were monitored in mice treated with anti-fla-a as compared to untreated mice. Bacterial dissemination and invasiveness were monitored by bacterial counts at the burn site and spleen. Three different timing regimens for anti-fla-a treatment were studied: (a) prophylaxis (pre-infection), (b) therapeutic (post-infection), and (c) combined mode. Results Combined regimen of anti-fla-a markedly improved survival of mice infected with P. aeruginosa from 6% to 96% ( p < 0.0001), similar to treatment with Imipenem. Furthermore, a significant improvement in survival was obtained when anti-fla-a was given prior to (75% survival) or post-infection (50% survival). It reduced bacterial load in the spleen ( p = 0.01), preventing bacterial sepsis. Conclusion Anti-fla-a is effective in reducing mortality and morbidity in murine P. aeruginosa -infected burn model.