Early increase of plasma homocysteine in sepsis patients with poor outcome

Mol Med. Nov-Dec 2010;16(11-12):498-504. doi: 10.2119/molmed.2010.00008. Epub 2010 Mar 26.


Moderate hyperhomocysteinemia is a well-established coronary risk factor that develops when dietary supply with folate and/or vitamin B(12) is inadequate. Recently, stimulated peripheral blood mononuclear cells were shown to produce homocysteine. Thus, the stimulated immune system may contribute to moderate hyperhomocysteinemia during certain diseases. Because multiple trauma and sepsis are accompanied by often strong inflammatory responses, we investigated whether hyperhomocysteinemia may develop in patients. Total homocysteine and cysteine concentrations were measured in 83 plasma specimens from 18 patients (14 men, 4 women; 15 posttrauma with sepsis and 3 with sepsis alone) every third day of follow-up. Finally results were compared with concentrations of cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6, the immune activation marker neopterin and the extent of tryptophan degradation as indicated by the kynurenine-to-tryptophan ratio (kyn/trp). Compared with baseline, average total homocysteine (P < 0.05, d 4-d 10) and cysteine (P < 0.05, d 7-d 13) concentrations increased during follow-up of patients. However, only the increase of homocysteine was related to the survival status: total homocysteine was significantly higher in nonsurvivors (P < 0.05, d 4 and d 10) than in survivors, whereas cysteine concentrations increased in both subgroups. Homocysteine correlated with kyn/trp but not with neopterin concentrations. Increase of total homocysteine is common in patients after trauma with unfavorable outcome. Because all patients received standardized enteral nutrition after the end of hypodynamic shock, inconsistent vitamin supply is unlikely to be the reason for hyperhomocysteinemia in some of the patients; rather, it is associated with a stronger proinflammatory response. Certainly, the number of patients in our study is still small and results can only be regarded as preliminary.

MeSH terms

  • Adult
  • Biomarkers / blood
  • Female
  • Follow-Up Studies
  • Homocysteine / blood*
  • Humans
  • Hyperhomocysteinemia / immunology*
  • Hyperhomocysteinemia / metabolism
  • Interleukin-6 / blood
  • Kynurenine / blood
  • Male
  • Middle Aged
  • Neopterin / blood
  • Sepsis / complications*
  • Sepsis / therapy*
  • Treatment Outcome
  • Tryptophan / blood
  • Tumor Necrosis Factor-alpha / blood
  • Young Adult


  • Biomarkers
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Homocysteine
  • Kynurenine
  • Neopterin
  • Tryptophan