Therapeutic efficacy of lysophosphatidylcholine in severe infections caused by Acinetobacter baumannii

• Published in: Antimicrobial agents and chemotherapy 2015-07, Vol.59 (7), p.3920-3924
• Main Authors: Smani, Younes, Domínguez-Herrera, Juan, Ibáñez-Martínez, José, Pachón, Jerónimo
• Format: Article
• Language: English
• Subjects: Acinetobacter baumannii; Acinetobacter Infections; Acinetobacter Infections - drug therapy; Acinetobacter Infections - microbiology; Acinetobacter Infections - mortality; Animals; Colony Count, Microbial; Cytokines - blood; Drug Resistance, Bacterial; Experimental Therapeutics; Female; Lung - microbiology; Lysophosphatidylcholines; Lysophosphatidylcholines - blood; Lysophosphatidylcholines - pharmacokinetics; Lysophosphatidylcholines - therapeutic use; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Pneumonia - microbiology; Sepsis - microbiology; Spleen - microbiology
• ISSN: 0066-4804; 1098-6596
• DOI: 10.1128/AAC.04986-14

Due to the significant increase in antimicrobial resistance of Acinetobacter baumannii, immune system stimulation to block infection progression may be a therapeutic adjuvant to antimicrobial treatment. Lysophosphatidylcholine (LPC), a major component of phospholipids in eukaryotic cells, is involved in immune cell recruitment and modulation. The aim of this study was to show if LPC could be useful for treating infections caused by A. baumannii. A. baumannii ATCC 17978 was used in this study. Levels of serum LPC and levels of the inflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), IL-1β, and IL-10 were determined by spectrophotometric assay and enzyme-linked immunosorbent assay (ELISA), respectively, using a murine peritoneal sepsis model in which mice were inoculated with 5.3 log CFU/ml of A. baumannii. The therapeutic efficacy of LPC against A. baumannii in murine peritoneal sepsis and pneumonia models was assessed for 48 h after bacterial infection. At early time points in the murine model of peritoneal sepsis caused by A. baumannii, LPC was depleted and was associated with an increase of inflammatory cytokine release. Preemptive therapy with LPC in murine peritoneal sepsis and pneumonia models markedly enhanced spleen and lung bacterial clearance and reduced the numbers of positive blood cultures and the mouse mortality rates. Moreover, treatment with LPC reduced proinflammatory cytokine production. These data demonstrate that LPC is efficacious as a preemptive treatment in experimental models of peritoneal sepsis and pneumonia caused by A. baumannii.