title: Physical exercise induces specific adaptations resulting in reduced organ injury and mortality during severe polymicrobial sepsis.
abstract: OBJECTIVE
  High physical activity levels are associated with wide-ranging health benefits, disease prevention, and longevity. In the present study, we examined the impact of regular physical exercise on the severity of organ injury and survival probability, as well as characteristics of the systemic immune and metabolic response during severe polymicrobial sepsis.
  
  
  METHODS
  Animal study.
  
  
  METHODS
  University laboratory.
  
  
  METHODS
  Male C57BL/6N mice.
  
  
  METHODS
  Mice were trained for 6 weeks by treadmill and voluntary wheel running or housed normally. Polymicrobial sepsis in mice was induced by injection of fecal slurry. Subsequently, mice were randomized into the following groups: healthy controls, 6 hours postsepsis, and 24 hours postsepsis.
  
  
  RESULTS
  Blood and organ samples were collected and investigated by measuring clinical chemistry variables, cytokines, plasma metabolites, and bacterial clearance. Organ morphology and damage were characterized by histological staining. Physical exercise improved survival and the ability of bacterial clearance in blood and organs. The release of pro- and anti-inflammatory cytokines, including interleukin-6 and interleukin-10, was diminished in trained compared to untrained mice during sepsis. The sepsis-associated acute kidney tubular damage was less pronounced in pretrained animals. By metabolic profiling and regression analysis, we detected lysophosphatidylcholine 14:0, tryptophan, as well as pimelylcarnitine linked with levels of neutrophil gelatinase-associated lipocalin representing acute tubular injury (corrected R=0.910; p<0.001). We identified plasma lysophosphatidylcholine 16:0, lysophosphatidylcholine 17:0, and lysophosphatidylcholine 18:0 as significant metabolites discriminating between trained and untrained mice during sepsis.
  
  
  CONCLUSIONS
  Regular physical exercise reduces sepsis-associated acute kidney injury and death. As a specific mechanism of exercise-induced adaptation, we identified various lysophosphatidylcholines that might function as surrogate for improved outcome in sepsis.
authors.affiliation: 1Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany. 2Department of Anesthesiology and Intensive Care, Jena University Hospital, Jena, Germany. 3Department of Experimental Radiology, Institute for Diagnostic and Interventional Radiology, Jena University Hospital, Jena, Germany. 4Department of Cardiothoracic Surgery, Jena University Hospital, Jena, Germany. 5Institute of Pathology, Hannover Medical School, Hannover, Germany. 6Department of Pharmacology and Toxicology, Jena University Hospital, Jena, Germany. 7Institute of Clinical Chemistry and Laboratory Diagnostics, Centralized Diagnostic Laboratory Services, Jena University Hospital, Jena, Germany. 8Institute of Medical Microbiology, Jena University Hospital, Jena, Germany. 9Department of Internal Medicine III, Jena University Hospital, Jena, Germany.
authors.forename: Maik
authors.initials: M
authors.lastname: Sossdorf
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Fischer
authors.forename: Stefan
authors.initials: S
authors.lastname: Meyer
authors.forename: Katja
authors.initials: K
authors.lastname: Dahlke
authors.forename: Bianka
authors.initials: B
authors.lastname: Wissuwa
authors.forename: Carolin
authors.initials: C
authors.lastname: Seidel
authors.forename: Andrea
authors.initials: A
authors.lastname: Schrepper
authors.forename: Clemens L
authors.initials: CL
authors.lastname: Bockmeyer
authors.forename: Amelie
authors.initials: A
authors.lastname: Lupp
authors.forename: Sophie
authors.initials: S
authors.lastname: Neugebauer
authors.forename: Diana
authors.initials: D
authors.lastname: Schmerler
authors.forename: Jürgen
authors.initials: J
authors.lastname: Rödel
authors.forename: Ralf A
authors.initials: RA
authors.lastname: Claus
authors.forename: Gordon P
authors.initials: GP
authors.lastname: Otto
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism / Q000382:microbiology / Q000517:prevention & control*; D000222:Adaptation, Physiological / Q000276:immunology; D000818:Animals; D060085:Coinfection / Q000150:complications* / Q000401:mortality; D016207:Cytokines / Q000378:metabolism; D048550:Hepatic Insufficiency / Q000378:metabolism / Q000382:microbiology / Q000517:prevention & control*; D055370:Lung Injury / Q000378:metabolism / Q000382:microbiology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010805:Physical Conditioning, Animal / Q000379:methods; D011897:Random Allocation; D018805:Sepsis / Q000150:complications* / Q000401:mortality; D016019:Survival Analysis
chemical_list: D016207:Cytokines