Open AccessAMRINONE AND THEOPHYLLINE DIFFERENTIALLY REGULATE CYTOKINE AND NITRIC OXIDE PRODUCTION IN ENDOTOXEMIC MICE
Author(s) -
Zoltán Németh,
György Haskó,
Csaba Szabó,
E. Sylvester Vizi
Publication year - 1997
Publication title -
shock
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.095
H-Index - 117
eISSN - 1540-0514
pISSN - 1073-2322
DOI - 10.1097/00024382-199705000-00010
Subject(s) - amrinone , nitric oxide , phosphodiesterase inhibitor , theophylline , chemistry , lipopolysaccharide , medicine , endocrinology , tumor necrosis factor alpha , cytokine , cyclic guanosine monophosphate , guanosine , nitric oxide synthase , nitrite , pharmacology , phosphodiesterase , biology , biochemistry , nitrate , enzyme , inotrope , organic chemistry
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 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.