title: Adenosine treatment attenuates cytokine interleukin-6 responses to endotoxin challenge in healthy volunteers.
abstract: Anti-inflammatory effects of adenosine were evaluated in two randomized, double-blind, placebo-controlled studies. In one study healthy male volunteers received no endotoxin (adenosine study, n = 10), in the other intravenous endotoxin (4 ng/kg, endotoxin study n = 11) was given. All subjects were treated with adenosine infusion (40 microg/kg/min) and placebo (saline) infusion in a crossover design. Heart rate, body temperature, blood pressure and plasma cytokines (tumor necrosis factor [TNF]-alpha, interleukin [IL]-6, IL-10, and soluble TNF receptors I and II), nitric oxide oxidation products, nitrite and nitrate, as well as superoxide anions were determined. There were no significant changes of any measured parameter after adenosine treatment alone. Endotoxin elicited clinical signs of an inflammatory reaction, prominent release of all cytokines and O2- synthesis by neutrophils (N-formyl-methionin-leucyl-phenylalanin-stimulated cells measured by cytochrome C reduction). The plasma IL-6 response to endotoxin was attenuated by adenosine, as IL-6 increased from 0.9 (0.8-1.6) to 1345 (743-1906) pg/mL (median; 25-75th percentiles) with adenosine infusion, and from 0.8 (0.5-1) to 1,959 (1,344-2,505) pg/mL with placebo (P = 0.0065). There was no significant influence of adenosine infusion on the other variables examined. In conclusion, systemic adenosine infusion counteracts the release of IL-6 in healthy volunteers, indicating an anti-inflammatory effect of adenosine which should be further explored.
authors.affiliation: Department of Anaesthesiology and Intensive Care, Center for Surgical Sciences, Huddinge University Hospital, Stockholm, Sweden.
authors.forename: Anne
authors.initials: A
authors.lastname: Soop
authors.forename: Cecilia
authors.initials: C
authors.lastname: Johansson
authors.forename: Paul
authors.initials: P
authors.lastname: Hjemdahl
authors.forename: Marianne
authors.initials: M
authors.lastname: Kristiansson
authors.forename: Hans
authors.initials: H
authors.lastname: Gyllenhammar
authors.forename: Nailin
authors.initials: N
authors.lastname: Li
authors.forename: Alf
authors.initials: A
authors.lastname: Sollevi
mesh_terms: D000241:Adenosine / Q000494:pharmacology*; D000328:Adult; D000700:Analgesics / Q000494:pharmacology; D045304:Cytochromes c / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000097:blood*; D004311:Double-Blind Method; D019075:Electrophoresis, Capillary; D004731:Endotoxins / Q000633:toxicity*; D004926:Escherichia coli; D006801:Humans; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D012016:Reference Values; D013481:Superoxides / Q000378:metabolism; D000093242:Interleukin-6 Inhibitors
chemical_list: D000241:Adenosine; D000700:Analgesics; D045304:Cytochromes c; D016207:Cytokines; D004731:Endotoxins; D009566:Nitrates; D009573:Nitrites; D013481:Superoxides; D000093242:Interleukin-6 Inhibitors