In:
Journal of Leukocyte Biology, Oxford University Press (OUP), Vol. 68, No. 1 ( 2000-07-01), p. 119-124
Abstract:
DBA/1 mice deficient in expressing the interferon-γ (IFN-γ) membrane receptor (IFN-γR KO mice) are more susceptible to collagen-induced arthritis (CIA) than wild-type mice, indicating that endogenous IFN-γ plays a protective role in the pathogenesis of CIA. In IFN-γR KO mice, nitric oxide (NO) production during CIA is impaired. Because NO is known to exert immunosuppressive and anti-inflammatory effects in certain model systems, the protective effect of IFN-γ might be mediated by NO. Here, we tested in wild-type mice whether inhibition of NO production by metabolic inhibitors, aminoguanidine (AG) and L-N-(1-iminoethyl)lysine (L-NIL), could mimic the ablation of the IFN-γ receptor. A high-dose regimen of AG supplied in the drinking water inhibited NO production, disease development, and anticollagen antibody production but was also associated with transient body weight loss. At a dose and time regimen that still inhibited NO production but did not cause body weight loss, AG failed to affect disease scores. Treatment with L-NIL, which more specifically than AG affects inducible NO production, caused a slight increase in anticollagen antibody production although not significantly affecting disease occurrence. These data indicate that the diminished capacity of the IFN-γR KO mice to produce NO following immunization with collagen is unlikely to account for their higher susceptibility to CIA.
Type of Medium:
Online Resource
ISSN:
1938-3673
,
0741-5400
DOI:
10.1189/jlb.68.1.119
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2000
detail.hit.zdb_id:
2026833-6
SSG:
12
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