Inflammatory cytokines play a pivotal role in rheumatoid arthritis (RA) and innovative non-pharmacological therapies aimed at limiting cytokine production are highly warranted. Recently, our group showed that healthy volunteers trained in an intervention developed by 'Iceman' Wim Hof were able to voluntarily attenuate the pro-inflammatory response during experimental human endotoxemia (a model of systemic inflammation elicited by administration of lipopolysaccharide \[LPS\] in healthy volunteers). Subjects trained in the intervention exhibited profound increases in plasma adrenaline levels, a rapid increase of an anti-inflammatory cytokine and subsequent attenuation of the pro-inflammatory response. The intervention consists of three elements, namely meditation, exposure to cold and breathing techniques. The meditation element is not likely to be involved. It was a very minor part of the training program and was not practiced during the endotoxemia experiments. Exposure to cold and the subsequent rewarming to normal body temperature may influence the inflammatory response through the release of immunomodulatory molecules like HSP-70. Also, exposure to cold can induce an ischemia-reperfusion-like state in the skin and peripheral tissue that is known to be involved in the downregulation of pro-inflammatory cytokines and upregulation of anti-inflammatory cytokines. The investigators anticipate that the third element, breathing techniques, is the major contributor to the anti-inflammatory effects of the intervention previously observed. The present study aims to explore the effects of the breathing technique ('strength ventilation'), the exposure to cold, and these two elements combined on the immune response during human endotoxemia. Elucidation of the relative contribution of the elements is of importance to establish a feasible, safe, and effective intervention for future use in patients. Objective: The primary objective of the present study is to determine the effects of the 'strength ventilation' breathing technique and exposure to cold, both separately and in combination, on the inflammatory response during human endotoxemia. To this end, a 2 by 2 design will be employed. Additionally, an evaluation of the influence of the cold exposure and breathing technique on pain thresholds and oxygen tension in the mitochondria will take place.
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circulating TNF-α
Timeframe: 8 hours