Iuvone T, D'Acquisto F, Carnuccio R, Di Rosa M
Department of Experimental Pharmacology, University of Naples Federico II, Italy.
Life Sci. 1996;59(13):PL207-11. doi: 10.1016/0024-3205(96)00425-0.
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.
