Adenosine infusion attenuates soluble RAGE in endotoxin-induced inflammation in human volunteers.
OBJECTIVE
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 microg 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-alpha, 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.


CONCLUSIONS
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.
Soop
A
A
Department for Clinical Science Intervention and Technology, Division of Anaesthesiology and Intensive Care, Karolinska University Hospital, Huddinge, Karolinska Institute, Stockholm, Sweden. anne.soop@karolinska.se
Sundén-Cullberg
J
J
Albert
J
J
Hållström
L
L
Treutiger
C-J
CJ
Sollevi
A
A
D000241:Adenosine / Q000008:administration & dosage / Q000276:immunology*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000276:immunology*; D001831:Body Temperature; D018592:Cross-Over Studies; D016207:Cytokines / Q000097:blood / Q000187:drug effects / Q000276:immunology*; D004311:Double-Blind Method; D004731:Endotoxins / Q000276:immunology; D006339:Heart Rate; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood / Q000187:drug effects / Q000276:immunology*; D012016:Reference Values; D052243:Resistin / Q000097:blood / Q000276:immunology*; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004731:Endotoxins; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D052243:Resistin; D009569:Nitric Oxide; D000241:Adenosine