title: Pre-treatment with probiotics prolongs survival after experimental infection by multidrug-resistant Pseudomonas aeruginosa in rodents: an effect on sepsis-induced immunosuppression.
abstract: Based on several randomised clinical studies indicating benefit from oral probiotic intake for the prevention of hospital-acquired infections in critically ill patients, this study aimed to explain the mechanism of action of probiotics for the prevention of lethal experimental infection by multidrug-resistant (MDR) Pseudomonas aeruginosa. Experiments using an Escherichia coli strain susceptible to all antimicrobials were also conducted. C57BL/6 mice were pre-treated intraperitoneally with sterile water for injection or Lactobacillus plantarum. Survival was recorded and mice were sacrificed for measurement of apoptosis and tissue bacterial overgrowth and for isolation and culture of splenocytes for cytokine production. Experiments were repeated after pre-treatment with a commercial preparation of four probiotics (L. plantarum, Lactobacillus acidophilus, Saccharomyces boulardii and Bifidobacterium lactis; LactoLevure(®)). Peripheral blood mononuclear cells (PBMCs) of healthy volunteers were stimulated by heat-killed P. aeruginosa following pre-treatment with medium or probiotics. Pre-treatment with L. plantarum significantly prolonged survival after challenge by either MDR P. aeruginosa (66.7% vs. 31.3%; P=0.026) or E. coli (56.0% vs. 12.0%, P=0.003). Survival benefit was even more pronounced when mice were pre-treated with LactoLevure(®). Tissue bacterial outgrowth and apoptosis of white blood cells and splenocytes were not altered. TNFα and IL-10 production by splenocytes of mice pre-treated with probiotic was increased and IFNγ production was decreased. Pre-treatment with LactoLevure(®) restored production of IL-17. Stimulation of human PBMCs after probiotic pre-treatment was accompanied by reduced gene expression of SOCS3. The results suggest that the protective effect of probiotics is mediated through prevention of sepsis-induced immunosuppression.
authors.affiliation: 4th Department of Internal Medicine, University of Athens, Medical School, Athens, Greece; 2nd Department of Propaedeutic Surgery, University of Athens, Medical School, Athens, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Machairas
authors.affiliation: 4th Department of Internal Medicine, University of Athens, Medical School, Athens, Greece.
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Pistiki
authors.affiliation: 4th Department of Internal Medicine, University of Athens, Medical School, Athens, Greece.
authors.forename: Dionyssia-Irini
authors.initials: DI
authors.lastname: Droggiti
authors.affiliation: 4th Department of Internal Medicine, University of Athens, Medical School, Athens, Greece.
authors.forename: Marianna
authors.initials: M
authors.lastname: Georgitsi
authors.affiliation: 4th Department of Internal Medicine, University of Athens, Medical School, Athens, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Pelekanos
authors.affiliation: 4th Department of Internal Medicine, University of Athens, Medical School, Athens, Greece.
authors.forename: Georgia
authors.initials: G
authors.lastname: Damoraki
authors.affiliation: 2nd Department of Propaedeutic Surgery, University of Athens, Medical School, Athens, Greece.
authors.forename: Grigorios
authors.initials: G
authors.lastname: Kouraklis
authors.affiliation: 4th Department of Internal Medicine, University of Athens, Medical School, Athens, Greece. Electronic address: egiamarel@med.uoa.gr.
authors.forename: Evangelos J
authors.initials: EJ
authors.lastname: Giamarellos-Bourboulis
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D024901:Drug Resistance, Multiple, Bacterial; D064368:Healthy Volunteers; D006801:Humans; D007108:Immune Tolerance; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008810:Mice, Inbred C57BL; D019936:Probiotics / Q000008:administration & dosage*; D011552:Pseudomonas Infections / Q000276:immunology / Q000628:therapy*; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D018805:Sepsis / Q000276:immunology / Q000628:therapy*; D016019:Survival Analysis
chemical_list: D016207:Cytokines
keywords: Interleukin-10; Probiotics; Pseudomonas aeruginosa; SOCS3; Sepsis; Tumour necrosis factor-alpha