Skip to main content
Journal cover image

Reduction of NOS2 overexpression in rheumatoid arthritis patients treated with anti-tumor necrosis factor alpha monoclonal antibody (cA2).

Publication ,  Journal Article
Perkins, DJ; St Clair, EW; Misukonis, MA; Weinberg, JB
Published in: Arthritis Rheum
December 1998

OBJECTIVE: Peripheral blood mononuclear cells (PBMC) from patients with rheumatoid arthritis (RA) have increased expression of nitric oxide synthase type 2 (NOS2) protein and enhanced formation of nitric oxide (NO) that correlate with disease activity. NO may play a role in the inflammation of RA. Treatment of RA patients with a chimeric monoclonal antibody against tumor necrosis factor alpha (TNFalpha; cA2) results in clinical improvement in the majority of patients. The present study was designed to determine if cA2 therapy decreases PBMC NOS2 protein expression and NOS enzyme activity in RA patients. METHODS: RA patients receiving background oral methotrexate participated in a double-blind, placebo-controlled clinical trial in which they were randomly assigned to receive a single infusion of either placebo or cA2 at 5, 10, or 20 mg/kg. NOS2 protein and NOS enzyme activity were measured in PBMC at baseline and 4 weeks following cA2 therapy. These results were compared with the degree of clinical change in disease activity. RESULTS: At baseline, elevated levels of NOS2 protein and NOS enzyme activity were more frequently detected in PBMC from RA patients than in those from healthy controls. Treatment of the RA patients with cA2 significantly reduced NOS2 protein expression and NOS enzyme activity. Changes in NOS activity following treatment correlated significantly with changes in the number of tender joints. CONCLUSION: These results indicate that TNFalpha likely plays an important role in enhancing NOS2 expression in RA, and that the antiinflammatory effects of cA2 treatment may be mediated by a reduction of NO overproduction.

Duke Scholars

Published In

Arthritis Rheum

DOI

ISSN

0004-3591

Publication Date

December 1998

Volume

41

Issue

12

Start / End Page

2205 / 2210

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Severity of Illness Index
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase
  • Middle Aged
  • Male
  • Leukocytes, Mononuclear
  • Infliximab
  • Humans
  • Female
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Perkins, D. J., St Clair, E. W., Misukonis, M. A., & Weinberg, J. B. (1998). Reduction of NOS2 overexpression in rheumatoid arthritis patients treated with anti-tumor necrosis factor alpha monoclonal antibody (cA2). Arthritis Rheum, 41(12), 2205–2210. https://doi.org/10.1002/1529-0131(199812)41:12<2205::AID-ART16>3.0.CO;2-Q
Perkins, D. J., E. W. St Clair, M. A. Misukonis, and J. B. Weinberg. “Reduction of NOS2 overexpression in rheumatoid arthritis patients treated with anti-tumor necrosis factor alpha monoclonal antibody (cA2).Arthritis Rheum 41, no. 12 (December 1998): 2205–10. https://doi.org/10.1002/1529-0131(199812)41:12<2205::AID-ART16>3.0.CO;2-Q.
Perkins DJ, St Clair EW, Misukonis MA, Weinberg JB. Reduction of NOS2 overexpression in rheumatoid arthritis patients treated with anti-tumor necrosis factor alpha monoclonal antibody (cA2). Arthritis Rheum. 1998 Dec;41(12):2205–10.
Perkins, D. J., et al. “Reduction of NOS2 overexpression in rheumatoid arthritis patients treated with anti-tumor necrosis factor alpha monoclonal antibody (cA2).Arthritis Rheum, vol. 41, no. 12, Dec. 1998, pp. 2205–10. Pubmed, doi:10.1002/1529-0131(199812)41:12<2205::AID-ART16>3.0.CO;2-Q.
Perkins DJ, St Clair EW, Misukonis MA, Weinberg JB. Reduction of NOS2 overexpression in rheumatoid arthritis patients treated with anti-tumor necrosis factor alpha monoclonal antibody (cA2). Arthritis Rheum. 1998 Dec;41(12):2205–2210.
Journal cover image

Published In

Arthritis Rheum

DOI

ISSN

0004-3591

Publication Date

December 1998

Volume

41

Issue

12

Start / End Page

2205 / 2210

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Severity of Illness Index
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase
  • Middle Aged
  • Male
  • Leukocytes, Mononuclear
  • Infliximab
  • Humans
  • Female