Mitochondrial function of immune cells in septic shock: A prospective observational cohort studyReportar como inadecuado




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Background

Reduced cellular ATP synthesis due to impaired mitochondrial function of immune cells may be a factor influencing the immune response in septic shock. We investigate changes in mitochondrial function and bioenergetics of human monocytes and lymphocyte subsets.

Methods

Thirty patients with septic shock were studied at ICU admission, after 24 and 48 hours, and after resolution of shock. Enzymatic activities of citrate synthase and mitochondrial complexes I, IV, and ATP synthase and ATP content of monocytes, T-cells and B-cells and pro-inflammatory IL-1β and IL-6 and anti-inflammatory IL-10 cytokine plasma concentrations were compared to samples from 20 healthy volunteers.

Results

Large variations in mitochondrial enzymatic activities of immune cells of septic patients were detected. In monocytes, maximum levels of citrate synthase activity in sepsis were significantly lower when compared to controls p = 0.021. Maximum relative enzymatic activity ratio relative to citrate synthase activity of complex I p<0.001, complex IV p = 0.017 and ATP synthase p<0.001 were significantly higher. In T-cells, maximum levels of citrate synthase p = 0.583 and relative complex IV p = 0.602 activity did not differ between patients and controls, whereas levels of relative complex I p = 0.006 and ATP synthase p = 0.032 were significantly higher in septic patients. In B-cells of patients, maximum levels of citrate synthase activity p = 0.004 and relative complex I p<0.001 were significantly higher, and mean levels of relative complex IV p = 0.042 lower than the control values, whereas relative ATP synthase activity did not differ p = 1.0. No significant difference in cellular ATP content was detected in any cell line p = 0.142–0.519. No significant correlations between specific cytokines and parameters of mitochondrial enzymatic activities or ATP content were observed.

Conclusions

Significant changes of mitochondrial enzymatic activities occur in human peripheral blood immune cells in septic shock when compared to healthy controls. Assessed sub-types of immune cells showed differing patterns of regulation. Total ATP-content of human immune cells did not differ between patients in septic shock and healthy volunteers.



Autor: Tobias M. Merz , Adriano J. Pereira, Roger Schürch, Joerg C. Schefold, Stephan M. Jakob, Jukka Takala, Siamak Djafarzadeh

Fuente: http://plos.srce.hr/



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