Endotoxemia-induced inflammation and the effect on the human brain

Abstract

IntroductionEffects of systemic inflammation on cerebral function are not clear, as both inflammation-induced encephalopathy as well as stress-hormone mediated alertness have been described.MethodsExperimental endotoxemia (2 ng/kg Escherichia coli lipopolysaccharide [LPS]) was induced in 15 subjects, whereas 10 served as controls. Cytokines (TNF-α, IL-6, IL1-RA and IL-10), cortisol, brain specific proteins (BSP), electroencephalography (EEG) and cognitive function tests (CFTs) were determined.ResultsFollowing LPS infusion, circulating pro- and anti-inflammatory cytokines, and cortisol increased (P < 0.0001). BSP changes stayed within the normal range, in which neuron specific enolase (NSE) and S100-β changed significantly. Except in one subject with a mild encephalopathic episode, without cognitive dysfunction, endotoxemia induced no clinically relevant EEG changes. Quantitative EEG analysis showed a higher state of alertness detected by changes in the central region, and peak frequency in the occipital region. Improved CFTs during endotoxemia was found to be due to a practice effect as CFTs improved to the same extent in the reference group. Cortisol significantly correlated with a higher state of alertness detected on the EEG. Increased IL-10 and the decreased NSE both correlated with improvement of working memory and with psychomotor speed capacity. No other significant correlations between cytokines, cortisol, EEG, CFT and BSP were found.ConclusionsShort-term systemic inflammation does not provoke or explain the occurrence of septic encephalopathy, but primarily results in an inflammation-mediated increase in cortisol and alertness.Trial registrationNCT00513110.

Systemic Lipopolysaccharide Administration-Induced Cognitive Impairments are Reversed by Erythropoietin Treatment in Mice

“…Also, it is well defined that acute inflammation induced by LPS or IL-1β injection causes memory deficits [24]. On the other hand, it is reported that hippocampal IL-1β overexpression impairs contextual and spatial long-term memory [24], while IL-10 inhibits LPSinduced sickness behavior and tribulations in hippocampal-dependent memory [27]. In the present study, we observed that IL-1β and MDA levels are increased in sepsis survivors, confirming previous studies demonstrating neuroinflammation and oxidative stress are important mediators in the sepsis induced cognition impairments.…”

How systemic inflammation modulates adenosine metabolism and adenosine receptor expression in humans in vivo

“…These trials are registered at the Clinical Trial Register (NCT00513110, NCT00783068, and NCT01091571) (9,10). In order to prevent confounding by the different pharmacological interventions in these trials, analyses were performed on data of placebotreated subjects only.…”

Peripheral T-lymphocyte and natural killer cell population imbalance is associated with septic encephalopathy in patients with severe sepsis

“…The S-100β protein has been previously employed as an indicator of astrocyte activation and injury, and as a marker for brain injury in SE (37,38); however, not all studies concur with this finding (39,40). In the present study, S-100β protein was significantly higher in SE patients, but regression analysis indicated that this is not the most reliable indicator for predicting SE, a finding that was consistent with previously conflicting findings (37)(38)(39)(40). Additional evaluation of the direct effect of brain injury to SE is required to clarify the most effective markers.…”

“…Reduced hepatic clearance and increased neurotoxic amino acids in sepsis associated with muscle proteolysis also contribute to the development of brain dysfunction (35,36). The S-100β protein has been previously employed as an indicator of astrocyte activation and injury, and as a marker for brain injury in SE (37,38); however, not all studies concur with this finding (39,40). In the present study, S-100β protein was significantly higher in SE patients, but regression analysis indicated that this is not the most reliable indicator for predicting SE, a finding that was consistent with previously conflicting findings (37)(38)(39)(40).…”