Amrinone and theophylline differentially regulate cytokine and nitric oxide production in endotoxemic mice

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

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Intracellular cyclic nucleotide levels play an important role in the regulation of several immunological processes. Since elevation of intracellular cyclic adenosine monophosphate and/or cyclic guanosine monophosphate concentration by inhibition of phosphodiesterase (PDE) is known to modulate the inflammatory response, we compared the effect of amrinone, an inhibitor of the PDE III isoenzyme, and of theophylline, a nonspecific PDE inhibitor, on the plasma tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), and nitric oxide response in mice to intraperitoneal injection of bacterial lipopolysaccharide (LPS). Intraperitoneal treatment of animals with amrinone (100 mg/kg) 30 min before LPS administration decreased both plasma IL-6 and IL-10 concentrations in the first phase of the response, but enhanced plasma levels of these cytokines in the second part. In contrast, pretreatment of the animals with theophylline (100 mg/kg) enhanced LPS-induced plasma IL-6 and IL-10 levels during the whole response. However, pretreatment with both PDE inhibitors resulted in a marked inhibition of LPS- evoked plasma concentrations of TNF-α and nitrite/nitrate (breakdown products of nitric oxide) throughout the response. This study demonstrates for the first time that amrinone and theophylline possess differential, but primarily anti-inflammatory, properties during LPS-induced systemic inflammation in the mouse.

Original languageEnglish (US)
Pages (from-to)371-375
Number of pages5
JournalShock
Volume7
Issue number5
StatePublished - 1997
Externally publishedYes

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Amrinone
Theophylline
Lipopolysaccharides
Nitric Oxide
Cytokines
Interleukin-10
Interleukin-6
Phosphodiesterase Inhibitors
Tumor Necrosis Factor-alpha
Type 3 Cyclic Nucleotide Phosphodiesterases
Cyclic Nucleotides
Phosphoric Diester Hydrolases
Nitrites
Intraperitoneal Injections
Nitrates
Isoenzymes
Anti-Inflammatory Agents
Inflammation

ASJC Scopus subject areas

  • Physiology
  • Critical Care and Intensive Care Medicine

Cite this

Amrinone and theophylline differentially regulate cytokine and nitric oxide production in endotoxemic mice. / Németh, Zoltán H.; Haskó, György; Szabo, Csaba; Vizi, E. Sylvester.

In: Shock, Vol. 7, No. 5, 1997, p. 371-375.

Research output: Contribution to journalArticle

Németh, Zoltán H. ; Haskó, György ; Szabo, Csaba ; Vizi, E. Sylvester. / Amrinone and theophylline differentially regulate cytokine and nitric oxide production in endotoxemic mice. In: Shock. 1997 ; Vol. 7, No. 5. pp. 371-375.
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