Hyperbaric oxygen protects from sepsis mortality via an interleukin-10-dependent mechanism.
OBJECTIVE
This study was performed to determine whether hyperbaric oxygen (HBO2) 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 HBO2 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 HBO2 protection in sepsis was dependent on IL-10 production.


METHODS
Prospective, experimental study.


METHODS
University experimental research laboratory.


METHODS
C57BL/6 and C57BL/6 IL-10 mice.


METHODS
Sepsis was induced by CLP. Mice were randomized to receive a 1.5-hr HBO2 treatment at either 1, 2.5, or 3 atmospheres absolute every 12 hrs or HBO2 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.


RESULTS
Survival was monitored for 100 hrs after CLP +/- HBO2 treatment. HBO2 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 HBO2-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 HBO2 at 2.5 atmospheres absolute every 12 hrs were not protected from CLP-induced mortality.


CONCLUSIONS
HBO2 may be protective in CLP sepsis within a window of oxygen dosing. The mechanism of HBO2 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 HBO2 treatment.
Buras
Jon A
JA
New England Inflammation and Tissue Protection Institute Consortium at Northeastern University, Boston, MA, USA.
Holt
Douglas
D
Orlow
Daniel
D
Belikoff
Bryan
B
Pavlides
Stavros
S
Reenstra
Wende R
WR
D000818:Animals; D015169:Colony Count, Microbial; D006931:Hyperbaric Oxygenation; D016753:Interleukin-10 / Q000378:metabolism*; D008070:Lipopolysaccharides; D017737:Macrophages, Peritoneal / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016016:Proportional Hazards Models; D011897:Random Allocation; D018805:Sepsis / Q000276:immunology / Q000382:microbiology / Q000628:therapy*; D016019:Survival Analysis
D008070:Lipopolysaccharides; D016753:Interleukin-10