The Effects of Concentration/Meditation on the Innate Immune Response During Human Endotoxemia
The innate immune response is the first line of defense against invading pathogens. Ideally, the inflammatory response is tightly regulated leading to both adequate protection to invading pathogens as well as limitation of an exuberant or unwanted immune response such as seen in sepsis or auto-immune diseases. It has become increasingly clear that the autonomic nervous system (ANS) and the innate immune response are intimately linked. Activation of the sympathetic division of ANS dampens inflammation via β2-adrenoceptors. On the other hand, in some cases, sympathetic drive can also stimulate the inflammatory response via α2-adrenoceptors. The parasympathetic branch of the ANS modulates the inflammatory response as well, since it was discovered that electrical stimulation of the efferent vagus nerve in rats greatly inhibits the innate immune response. Generally, the ANS is regarded as pure autonomic which can not be influenced by behavior. However, trough special concentration/mediation techniques mastered by certain individuals, it might be possible to modulate ANS activity. In addition, recent unpublished findings indicate that these concentration/meditation techniques can also influence the inflammatory response ex vivo.
In this study the investigators wish to investigate the effect of concentration/meditation on the innate immune response in vivo. In addition the investigators wish to elucidate the mechanism via which this effect is mediated. The investigators aim to use the so called human endotoxemia model. This model permits elucidation of key players in the immune response to a gram negative stimulus in vivo, therefore serving as a useful tool to investigate potential novel therapeutic strategies in a standardized setting.
Primary objective: The primary objective of the study is to determine the effect of concentration/meditation on the innate immune response induced by a lipopolysaccharide (LPS) challenge.
- To determine the effects of concentration/meditation on ANS activity. Electroencephalography (EEG), heart-rate variability (HRV), muscle sympathetic nerve activity and plasma concentrations of catecholamines will be measured for this purpose.
- To determine if concentration/meditation can attenuate (subclinical) renal damage known to occur during human endotoxemia, markers of proximal and distal tubular damage will be measured at various time points.
Innate Immune Response
Behavioral: Concentration / meditation
|Study Design:||Observational Model: Case-Only
Time Perspective: Prospective
|Official Title:||The Effects of Concentration/Meditation on the Innate Immune Response During|
- Change in Plasma TNF-alpha levels [ Time Frame: 0; 1; 1.5; 2; 3; 4; 6; 8; 12; 24 hrs after endotoxin administration ] [ Designated as safety issue: No ]Concentration of circulating TNF-alfa at certain timepoints.
- Change in plasma IL-6, IL-10 and IL-1ra levels and leukocyte counts [ Time Frame: 0; 1; 1.5; 2; 3; 4; 6; 8; 12; 24 hrs after endotoxin administration ] [ Designated as safety issue: No ]
circulating IL-6, IL-10 and IL-1ra levels at certain timepoints.
Leucocyte count and differentiation will be measured
- Change in measures of autonomous nervous system activity [ Time Frame: at regulare intervals before and during endotoxemia ] [ Designated as safety issue: No ]
- Electroencephalography (EEG)
- Heart rate variability (HRV)
- Plasma cathecholamines
- Muscle sympathetic nerve activity (MSNA)
- Change in markers of subclinical renal tubular damage [ Time Frame: before and at 0-3, 3-6, 6-9, 9-12 and 12-24 hrs after endotoxemia ] [ Designated as safety issue: No ]
determination of markers in urine collected within the above mentioned intervals.
GSTA1-1 will be used as marker for proximal tubular damage GSTP1-1 will be used as marker for distal tubular damage
|Study Start Date:||March 2011|
|Study Completion Date:||May 2011|
|Primary Completion Date:||April 2011 (Final data collection date for primary outcome measure)|
Concentration / meditation
The subject will try to influence the innate immune response by concentration / meditation in advance of and during endotoxemia
Behavioral: Concentration / meditation
from 30 minutes before endotoxin administration to 1,5 hrs after endotoxin administration the subject is concentrating / meditating with the goal to influence the innate immune responseDrug: lipopolysaccharide
lipopolysaccharide 2ng/kg intravenously
|Radboud University Nijmegen Medical Centre|
|Nijmegen, Gelderland, Netherlands, 6511HB|
|Principal Investigator:||Peter Pickkers, MD, PhD||Radboud University|