1. Suppression of adjuvant arthritis and synovial macrophage inducible nitric oxide by N-iminoethyl-L-ornithine, a nitric oxide synthase inhibitor
- Author
-
L L, Santos, E F, Morand, Y, Yang, P, Hutchinson, and S R, Holdsworth
- Subjects
Male ,Ornithine ,Macrophages ,Synovial Membrane ,Nitric Oxide ,Arthritis, Experimental ,Rats ,Rats, Sprague-Dawley ,Animals ,Hypersensitivity, Delayed ,Enzyme Inhibitors ,Inflammation Mediators ,Nitric Oxide Synthase ,Skin - Abstract
Nitric oxide (NO.) is a pro-inflammatory effector molecule in certain inflammatory diseases, including arthritis. We investigated the production of NO. by adjuvant arthritis (AA) synovial macrophages, and studied the effects of a NO. synthase inhibitor. N-iminoethyl-L-ornithine (L-NIO). Compared to control rats, rats treated with L-NIO in vivo exhibited significantly lower articular index (p0.05), paw volume (p0.05), and synovial fluid cell count (p0.05). No effect on cutaneous delayed-type hypersensitivity to the disease-initiating antigen was observed. Inducible NO. synthase (iNOS) was detected in AA synovial macrophages, and cultured AA synovial macrophage iNOS levels were increased by a factor of 138 +/- 17% (p0.01) by 1 microgram/ml LPS in vitro. Constitutive NO. production by AA synovial macrophages (43 +/- 1 nmol/10(5) cells/24 h) was significantly inhibited by 10 nM L-NIO in vitro (32 +/- 0.5, p0.01). NO. production induced by 1 microgram/ml LPS (48 +/- 2) was also decreased by L-NIO (39 +/- 2, p0.05). In vivo L-NIO treatment also inhibited alveolar macrophage NO. production (p0.05). The ability of L-NIO to decrease iNOS-mediated synovial macrophage NO. production and inhibit the clinical parameters of AA implicate macrophage-derived NO. in the pathogenesis of this disease.
- Published
- 1997