Effects of N(G)-Nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthesis, on IL-2-induced LAK cell generation in vivo and in vitro in healthy and tumor-bearing mice

Cellular Immunology
A Orucevic, P K Lala

Abstract

We had earlier shown that therapy with N(G)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthesis, had antitumor and antimetastatic effects in C3-L5 mammary adenocarcinoma-bearing mice. When combined with interleukin-2 (IL-2) therapy, L-NAME augmented antitumor effects of IL-2. In the present study, we tested whether the L-NAME effects were due, at least in part, to a potentiation of antitumor cytotoxicity of host effector cells. We examined the effects of L-NAME on IL-2-induced generation of antitumor cytotoxicity in vivo and in vitro in splenocytes of healthy and C3-L5 tumor-bearing C3H/HeJ mice, using 51Cr release assay. IL-2 treatment, in vivo or in vitro, markedly stimulated splenocyte tumoricidal activity against NK-sensitive (YAC-1) and -resistant (C3-L5) targets, accompanied with an increase in NO production measured in the serum or culture medium. Addition of L-NAME to IL-2 therapy blocked IL-2-induced NO production in vivo and improved IL-2-induced splenocyte cytotoxicity as well as tumor regression. Addition of L-NAME in vitro also reduced IL-2-induced NO production in the medium and enhanced IL-2 induced cytotoxicity of splenocytes of healthy but not tumor-bearing mice. These results re...Continue Reading

Citations

Jul 22, 2006·Proceedings of the National Academy of Sciences of the United States of America·Marcella FerlitoCharles J Lowenstein
Dec 14, 2007·Immunopharmacology and Immunotoxicology·Sonja GasicMiodrag Colic
Mar 21, 2002·The Lancet Oncology·P K Lala, C Chakraborty
Jul 26, 2006·British Journal of Pharmacology·Susana E MorenoBernardo Boris Vargaftig
Jan 18, 2007·The Journal of Pharmacy and Pharmacology·David Hirst, Tracy Robson
Jun 3, 2021·Medical Sciences : Open Access Journal·Francisco TustumiEdno Tales Bianchi

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