Elsevier

Life Sciences

Volume 59, Issue 13, 23 August 1996, Pages PL207-PL211
Life Sciences

Pharmacology letter accelerated communication
Nitric oxide inhibits LPS-induced tumor necrosis factor synthesis in vitro and in vivo

https://doi.org/10.1016/0024-3205(96)00425-0Get rights and content

Abstract

The effect of nitric oxide (NO) on LPS-stimulated TNF-α synthesis has been studied in vitro and in vivo. The synthesis of TNF-α in J774 macrophages stimulated with LPS (0.l μg/ml) was increased in concentration-related fashion by NO synthase inhibitor L-NMMA (3-30-300 μM) and reduced by either L-arginine (3-30-300 μM) or the NO donor SIN-1 (1-10-1OOμM). The level of TNF-α 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-α synthesis suggesting an important regulatory link between NO and TNF-α in pathological processes.

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