Early Increase of Plasma Homocysteine in Sepsis Patients with Poor Outcome

Abstract

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.

Neopterin as an Effect Modifier of the Cardiovascular Risk Predicted by Total Homocysteine: A Prospective 2‐Cohort Study

“…Also, homocysteine accumulates in parallel with neopterin upon stimulation of human peripheral blood mononuclear cells, indicating an additional direct link between immune activation and elevated tHcy. This finding is further substantiated by recent observations in sepsis patients, in whom tHcy increased only in nonsurvivors as compared with survivors …”

“…This finding is further substantiated by recent observations in sepsis patients, in whom tHcy increased only in nonsurvivors as compared with survivors. 41…”

Pyridoxal-5′-phosphate deficiency is associated with hyperhomocysteinemia regardless of antioxidant, thiamine, riboflavin, cobalamine, and folate status in critically ill patients

“…2B). Throughout the last decade, it has been shown that the prevalence of HHcy in critically ill patients varies from 16% to 55% [10,14,24,25], taking into account the different reference plasma Hcy levels used (!10 or !15 mmol). In our study we took 15 mmol/L as the hospital reference value, according to normal values considered by the American Heart Association (5e15 mmol/L) [26].…”

Association between ischemia-modified albumin, homocysteine, vitamin B12 and folic acid in patients with severe sepsis

“…Thus, the stimulated immune system may contribute to moderate hyperhomocysteinemia during certain diseases. Multiple trauma and sepsis are often accompanied by strong infl ammatory responses (18) .…”