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Adenosine infusion attenuates soluble RAGE in endotoxin‐induced inflammation in human volunteers
Author(s) -
Soop A.,
SundénCullberg J.,
Albert J.,
Hållström L.,
Treutiger C.J.,
Sollevi A.
Publication year - 2009
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/j.1748-1716.2009.01985.x
Subject(s) - adenosine , placebo , nitric oxide , medicine , crossover study , nitrite , pharmacology , endocrinology , chemistry , nitrate , alternative medicine , organic chemistry , pathology
Aim: To evaluate possible anti‐inflammatory effects of pre‐treatment with adenosine in a human experimental inflammatory model. Methods: The study design was double‐blind, crossover, placebo‐controlled and randomized. In the Intensive Care Unit of a university hospital, 16 healthy male volunteers were treated for 5.5 h with infusions of adenosine 40 μg kg −1 min −1 or placebo. Thirty minutes after the start of adenosine or placebo, 2 ng kg −1 E‐Coli endotoxin was administered. Heart rate, body temperature, blood pressure, plasma cytokines (TNF‐α, IL‐6 and IL‐10), soluble RAGE and resistin, exhaled nitric oxide and nitrite/nitrate in urine were determined. Results: Endotoxin elicited the expected clinical signs of an inflammatory reaction (tachycardia, fever) and led to prominent release of the cytokines studied ( P < 0.001). Resistin in plasma increased after endotoxin ( P < 0.001). After placebo treatment, soluble RAGE (sRAGE) in plasma increased 5 h after the endotoxin challenge ( P < 0.001) but not after adenosine. After placebo, orally exhaled NO increased with a peak at 4 h ( P < 0.001), although there was no statistically significant difference between the two treatments. Nitrite/nitrate in urine ( n = 11) did not differ between adenosine and placebo treatments. Conclusion: In conclusion, adenosine infusion starting before endotoxin challenge in humans attenuated sRAGE significantly but otherwise had no clear anti‐inflammatory effect. Adenosine as a potential anti‐inflammatory treatment in humans needs further study, including use of higher doses. The mechanism underlying the effect of adenosines on sRAGE remains unknown.