AIMS: Sepsis which is the leading cause of death in intensive care units is usually related to the number and the severity of organ failure, but the mechanisms remain to be fully established. Findings of microvascular flow abnormalities, decreased oxygen consumption and elevated tissue oxygen tensions suggest that problems may lay in cellular oxygen utilization rather than in oxygen delivery per se. Several serum factors, released during sepsis syndrome, might be involved in induction of cytopathic hypoxia and increase of cellular oxidative stress. MAIN METHODS: Human fibroblast cultures were incubated 12h with 10% v/v severe septic patients' sera and measurements were carried out on cellular oxygen consumption, mitochondrial respiratory enzymes activity, H(2)O(2) generation and serum levels of cytokines/chemokines by multiplex assay. KEY FINDINGS: In fibroblast cultures a significant depression of cellular respiration and activity of mitochondrial complexes and increased H(2)O(2) production was observed after incubation with septic sera showing increased levels of TNFα, IL-1β and IL-6. SIGNIFICANCE: During sepsis syndrome some increased cytokines might target specific mitochondrial enzymes inducing an impairment of cellular energy metabolism leading to multiple organ failure.
AIMS: Sepsis which is the leading cause of death in intensive care units is usually related to the number and the severity of organ failure, but the mechanisms remain to be fully established. Findings of microvascular flow abnormalities, decreased oxygen consumption and elevated tissue oxygen tensions suggest that problems may lay in cellular oxygen utilization rather than in oxygen delivery per se. Several serum factors, released during sepsis syndrome, might be involved in induction of cytopathic hypoxia and increase of cellular oxidative stress. MAIN METHODS:Human fibroblast cultures were incubated 12h with 10% v/v severe septic patients' sera and measurements were carried out on cellular oxygen consumption, mitochondrial respiratory enzymes activity, H(2)O(2) generation and serum levels of cytokines/chemokines by multiplex assay. KEY FINDINGS: In fibroblast cultures a significant depression of cellular respiration and activity of mitochondrial complexes and increased H(2)O(2) production was observed after incubation with septic sera showing increased levels of TNFα, IL-1β and IL-6. SIGNIFICANCE: During sepsis syndrome some increased cytokines might target specific mitochondrial enzymes inducing an impairment of cellular energy metabolism leading to multiple organ failure.
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