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

Shock
Z H NémethE S Vizi

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-alpha (TNF-alpha), 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-alpha and nitrite/nitrate (breakdown products of nitric oxide) throughout the ...Continue Reading

Citations

May 15, 2002·Antioxidants & Redox Signaling·Leo E Otterbein
Aug 18, 2000·The Journal of Surgical Research·W SchmidtH Schmidt
Sep 30, 2000·Journal of Critical Care·W SchmidtH Schmidt
Jun 19, 2004·International Archives of Allergy and Immunology·Koichiro MatsumotoYoichi Nakanishi
Feb 9, 2010·Immunopharmacology and Immunotoxicology·Marianna Szczypka, Bozena Obmińska-Mrukowicz

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