Hyperbaric oxygen protects from sepsis mortality via an interleukin-10-dependent mechanism
| Autor: | Wende R. Reenstra, DE Holt, Jon A. Buras, DL Orlow, Bryan Belikoff, Stavros Pavlides |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Lipopolysaccharides
Resuscitation Lipopolysaccharide medicine.medical_treatment Colony Count Microbial Pharmacology Critical Care and Intensive Care Medicine Sepsis chemistry.chemical_compound Mice Random Allocation Intensive care Medicine Animals Proportional Hazards Models Mice Knockout Hyperbaric Oxygenation biology business.industry Peritoneal fluid medicine.disease Survival Analysis Interleukin-10 Mice Inbred C57BL Interleukin 10 Cytokine chemistry Integrin alpha M Immunology biology.protein Macrophages Peritoneal business |
| Zdroj: | Critical care medicine. 34(10) |
| ISSN: | 0090-3493 |
| Popis: | Objective: This study was performed to determine whether hyperbaric oxygen (HBO 2 ) therapy is protective in cecal ligation and puncture (CLP)-induced sepsis and if protection is dependent on oxygen dosing. We also wished to determine whether HBO 2 affected bacterial clearance or altered macrophage production of interleukin-10 (IL-10)s in the setting of CLP sepsis. Finally, we wished to determine whether the mechanism of HBO 2 protection in sepsis was dependent on IL-10 production. Design: Prospective, experimental study. Setting: University experimental research laboratory. Subjects: C57BL/6 and C57BL/6 IL-10 -/- mice. Interventions: Sepsis was induced by CLP. Mice were randomized to receive a 1.5-hr HBO 2 treatment at either 1, 2.5, or 3 atmospheres absolute every 12 hrs or HBO 2 at 2.5 atmospheres absolute every 24 hrs. Mice were also harvested at 24 hrs for determination of bacterial load and isolation and study of CD11b + peritoneal macrophages. Measurements and Main Results: Survival was monitored for 100 hrs after CLP ± HBO 2 treatment. HBO 2 significantly improved survival when administered at 2.5 atmospheres absolute every 12 hrs. Other treatment schedules were not protective, and treatment at 3.0 atmospheres absolute significantly worsened survival outcome. Bacterial load was significantly reduced in splenic homogenates but not peritoneal fluid at 24 hrs. Macrophages isolated from HBO 2 -treated mice demonstrated enhanced IL-10 secretion in response to lipopolysaccharide as compared with CLP controls. Mice genetically deficient in IL-10 expression treated with HBO 2 at 2.5 atmospheres absolute every 12 hrs were not protected from CLP-induced mortality. Conclusion: HBO 2 may be protective in CLP sepsis within a window of oxygen dosing. The mechanism of HBO 2 protection may be potentially linked in part to expression of IL-10, as peritoneal macrophages demonstrated enhanced IL-10 expression and IL-10 -/- mice were not protected by HBO 2 treatment. |
| Databáze: | OpenAIRE |
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