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Endocannabinoids anandamide and 2- arachidonoylglycerol in sepsis

BACKGROUND-AIM Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. The incidence that continues to rise, high mortality and lack of early biomarkers to accurately identify disease processes, still represent a great challenge in sepsis diagnosis and treatment. The endocannabinoid system is an evolutionarily conserved lipid signaling system. Two main endocannabinoids (ECs) are anandamide (AEA) and 2-arachidonoylglycerol (2-AG). There is growing in-vitro evidence that ECs are released in response to inflammatory stimuli and that the endocannabinoid system may have an important role in sepsis. This study aimed to determine the plasma concentration of AEA and 2- AG in septic patients at the admission point and to evaluate their association with mortality in sepsis. METHODS A total of 106 septic patients (male: 40%) aged >18 were included in this study. 16 subjects (male: 50%) matched in age and comorbidity were enrolled as a control group. Septic patients were divided into two groups based on mortality outcome: a group of survivors (N=53) and a group of non-survivors (N=53). EDTA-plasma sample was collected upon admission to the hospital and AEA and 2-AG concentrations were determined. The difference in EC concentrations between males and females was assessed using the Mann-Whitney U test and the difference between two septic patients groups and control subjects was assessed using the Kruskal-Wallis test. RESULTS Median values of AEA and 2-AG concentrations in control subjects were 1.13 (0.67 – 1.73) μg/L and 1.53 (0.92-3.85) μg/L, respectively. There was no significant difference between males and females. At admission point, AEA and 2-AG levels in survivors were 5.04 (3.74-6.75) μg/L and 8.40 (5.01-22.25) μg/L and in non-survivors 7.25 (4.28-15-95) μg/L and 8.35 (3.28-29.34) μg/L, respectively, but there was no significant difference between two groups. We observed a significantly higher concentration of AEA and 2-AG in survivors and non-survivors when compared to control subjects (P<0.001). In sepsis, AEA levels were on average 5-fold higher and 2-AG levels 16-fold higher than normal. CONCLUSIONS Plasma concentration of ECs AEA and 2-AG in sepsis are elevated early at the admission point but did not differentiate the mortality outcome.

Endocannabinoids, anandamide, 2-arachidonoylglycerol, sepsis

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