Changes of lymph metabolites in a rat model of sepsis induced by cecal ligation and puncture

J Trauma Acute Care Surg. 2012 Dec;73(6):1545-52. doi: 10.1097/TA.0b013e31826fc9e7.

Abstract

Background: Sepsis is a clinical syndrome defined by a systemic response to infection and remains a prevalent clinical challenge. The underlying pathophysiology of sepsis is poorly understood. Using a metabolomic method, the present study observed changes in lymph composition during sepsis in a septic model in an attempt to find out new biomarkers for the early diagnosis and treatment of sepsis.

Methods: Adult male Sprague-Dawley rats underwent cecal ligation and puncture. Blood samples were obtained via the lateral caudal vein, and lymph was obtained from the thoracic duct. Cytokines were measured in plasma and lymph samples by enzyme-linked immunosorbent assay at different time points after cecal ligation and puncture. Rat lymph samples were analyzed by high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Multivariate analysis was used to profile potential biomarkers in rat septic lymph samples.

Results: Plasma and lymph tumor necrosis factor α, interleukin 1β, and interleukin 6 levels were elevated in septic group as compared with the control. Of the 10 characteristic metabolites identified in the septic model, six (palmitoyl-L-carnitine, creatinine, phenylalanine, isonicotinic acid, choline, and 5-azacytidine) were high, and four (1-O-Hexadecyl-2-lyso-glycero-3-phosphorylcholine, alanine, 4-amino-5-hydroxymethyl-2-methylpyrimidine, and asymmetric dimethylarginine) were low.

Conclusion: These biomarkers were mainly involved in energy metabolism and vascular tone and may prove beneficial to distinguish sepsis from other inflammatory conditions or predict outcomes.

MeSH terms

  • Animals
  • Biomarkers / analysis
  • Cecum / injuries*
  • Cytokines / analysis
  • Disease Models, Animal
  • Interleukin-1beta / analysis
  • Interleukin-6 / analysis
  • Lymph / chemistry*
  • Lymph / physiology
  • Male
  • Metabolomics
  • Mice
  • Rats
  • Rats, Sprague-Dawley
  • Sepsis / immunology
  • Sepsis / metabolism
  • Sepsis / physiopathology*
  • Tumor Necrosis Factor-alpha / analysis

Substances

  • Biomarkers
  • Cytokines
  • Interleukin-1beta
  • Interleukin-6
  • Tumor Necrosis Factor-alpha