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The effect of nitric oxide (NO) on LPS-stimulated TNF-alpha synthesis has been studied in vitro and in vivo. The synthesis of TNF-alpha in J774 macrophages stimulated with LPS (0.1 microgram/ml) was increased in concentration-related fashion by NO synthase inhibitor L-NMMA (3-30-300 microM) and reduced by either L-arginine (3-30-300 microM) or the NO donor SIN-1 (1-10-100 microM). The level of TNF-alpha in the serum of LPS-challenged rats (6mg/kg/i.p.) was increased in animals pre-treated s.c. with L-NMMA (10 and 50mg/kg) and reduced in those given L-arginine (100 and 300mg/kg). These results show a negative feedback mechanism exhibited by NO on TNF-alpha synthesis suggesting an important regulatory link between NO and TNF-alpha in pathological processes.
T Iuvone, and
F D'Acquisto, and
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M Di Rosa
July 1999,
International journal of immunopharmacology,
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December 1998,
European cytokine network,
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February 1993,
Surgery,
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October 1994,
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T Iuvone, and
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April 2000,
American journal of physiology. Lung cellular and molecular physiology,
T Iuvone, and
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May 2000,
Proceedings of the National Academy of Sciences of the United States of America,
T Iuvone, and
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T Iuvone, and
F D'Acquisto, and
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T Iuvone, and
F D'Acquisto, and
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January 2002,
Brain research. Developmental brain research,
