An agonist of adenosine A3 receptors decreases interleukin-12 and interferon-γ production and prevents lethality in endotoxemic mice

György Haskó, Zoltán H. Németh, E. Sylvester Vizi, Andrew L. Salzman, Csaba Szabo

Research output: Contribution to journalArticle

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Abstract

We have recently observed that the selective adenosine A3 receptor agonist N6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (IB-MECA) augments interleukin-10 and inhibits tumor necrosis factor-α production in endotoxemic mice. In the present study, we extended our investigations into the effect of this compound on the bacterial lipopolysaccharide (endotoxin)-induced inflammatory response in the BALB/c, as well as in the C57BL/6 interleukin-10(+/+) and the interleukin-10 deficient C57BL/6 interleukin-10(0/0) mice strains. In the BALB/c mice, i.p. pre-treatment with IB-MECA (0.2 and 0.5 mg/kg) decreased lipopolysaccharide (60 mg/kg i.p.)-induced plasma levels of interleukin-12 (p40 and p70), interferon-γ, and nitrite/nitrate (breakdown products of nitric oxide (NO)). On the other hand, pre-treatment with this compound failed to influence lipopolysaccharide-induced plasma interleukin-1α, interleukin-6, and corticosterone concentrations. Similar to its effect in BALB/c mice, IB-MECA enhanced the release of interleukin-10 in the C57BL/6 interleukin-10(+/+) mice. Furthermore, IB-MECA inhibited the production of interleukin-12, interferon-γ, and NO in both the C57BL/6 interleukin-10(+/+) and C57BL/6 interleukin-10(0/0) mice, suggesting that the inhibition of pro-inflammatory cytokine production by this compound is independent of the increased release of interleukin-10. Finally, pre-treatment with this compound protected mice against lipopolysaccharide (60 mg/kg i.p.)-induced lethality. These results indicate that stimulation of adenosine A3 receptors has potent anti-inflammatory effects and may represent a potential strategy in the treatment of septic shock and other inflammatory diseases. Copyright (C) 1998 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)261-268
Number of pages8
JournalEuropean Journal of Pharmacology
Volume358
Issue number3
DOIs
StatePublished - Oct 9 1998
Externally publishedYes

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Adenosine A3 Receptor Agonists
Interleukin-12
Interleukin-10
Interferons
Lipopolysaccharides
Nitric Oxide
Adenosine A3 Receptors
Septic Shock
Corticosterone
Nitrites
Interleukin-1
Endotoxins
Nitrates
Adenosine
Interleukin-6
Anti-Inflammatory Agents
Tumor Necrosis Factor-alpha

Keywords

  • Cytokine
  • Inflammation
  • Inflammatory mediator
  • Lipopolysaccharide
  • Nitric oxide (NO)
  • Shock

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

An agonist of adenosine A3 receptors decreases interleukin-12 and interferon-γ production and prevents lethality in endotoxemic mice. / Haskó, György; Németh, Zoltán H.; Vizi, E. Sylvester; Salzman, Andrew L.; Szabo, Csaba.

In: European Journal of Pharmacology, Vol. 358, No. 3, 09.10.1998, p. 261-268.

Research output: Contribution to journalArticle

Haskó, György ; Németh, Zoltán H. ; Vizi, E. Sylvester ; Salzman, Andrew L. ; Szabo, Csaba. / An agonist of adenosine A3 receptors decreases interleukin-12 and interferon-γ production and prevents lethality in endotoxemic mice. In: European Journal of Pharmacology. 1998 ; Vol. 358, No. 3. pp. 261-268.
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