Leflunomide reduces nitric oxide production in patients with active rheumatoid arthritis

Reddy, S. Vijaya Bhaskar, Wanchu, Ajay, Khullar, Madhu, Govindrajan, S and Bambery, Pradeep (2005) Leflunomide reduces nitric oxide production in patients with active rheumatoid arthritis. International Immunopharmacology, 5 6: 1085-1090. doi:10.1016/j.intimp.2004.11.013


Author Reddy, S. Vijaya Bhaskar
Wanchu, Ajay
Khullar, Madhu
Govindrajan, S
Bambery, Pradeep
Title Leflunomide reduces nitric oxide production in patients with active rheumatoid arthritis
Journal name International Immunopharmacology   Check publisher's open access policy
ISSN 1567-5769
1878-1705
Publication date 2005-06
Sub-type Article (original research)
DOI 10.1016/j.intimp.2004.11.013
Volume 5
Issue 6
Start page 1085
End page 1090
Total pages 6
Place of publication Oxford, United Kingdom
Publisher Elsevier
Language eng
Formatted abstract
Objectives:
Leflunomide is an immunomodulatory agent that was recently approved for the treatment of rheumatoid arthritis (RA). The mechanism of action is not fully understood. Nitric oxide (NO) plays an important role in the pathogenesis of RA. Leflunomide has been shown to cause cell specific inhibition of inducible nitric oxide synthase (iNOS) activation in animal models. We carried out this study to determine if there was alteration in NO production in patients with RA.

Methods:
An 8-week open label study was carried out on patients with adult onset active RA. We measured levels of nitrite and citrulline spectrophotometrically as surrogate markers of NO production. Within-patient serum levels of nitrite and citrulline were compared with leflunomide therapy at three points of time (at 0, 4 and 8 weeks of therapy).

Results:
Thirty-three patients with active RA were enrolled for this study. These patients were a subset of 63 individuals who are studied for clinical efficacy of leflunomide. Three patients were lost to follow-up. Median nitrite levels were 817.2 (nmol/ml) at the start of therapy and this declined to 440.9 nmol/ml and 301.1 nmol/ml at 4 and 8 weeks of therapy. Median citrulline levels were 649.3 nmol/ml at the start of the study, which declined to 549.2 nmol/ml and 485.4 nmol/ml at 4 and 8 weeks, respectively. Statistically significant decrease in median values for serum nitrite and citrulline levels was documented after 4 weeks of leflunomide therapy (p<0.01), which was sustained at 8 weeks (p<0.01), although there was no further fall between 4 and 8 weeks (p>0.1).

Conclusions:
Leflunomide inhibits nitric oxide production in patients with active RA. Inhibition of NO synthesis may be one of the mechanisms responsible for the immunomodulatory activity of leflunomide.
Keyword leflunomide
nitric oxide
rheumatoid arthritis
Necrosis-Factor-Alpha
Synthase
Activation
Metabolite
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: ERA 2012 Admin Only
School of Medicine Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 14 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 17 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Mon, 16 Jan 2012, 11:49:49 EST by System User on behalf of School of Medicine