| Abstract | Anti-CD4 treatment is reported to prevent collagen-induced arthritis if administered before the onset of clinical disease but has relatively little effect on established arthritis. In contrast, we have recently shown that anti-tumor necrosis factor alpha/beta (TNF) treatment reduces the severity of established arthritis. We now study the effect of combined administration of anti-CD4 monoclonal antibody (YTS 191.1.2/YTA 3.1.2) and anti-TNF monoclonal antibody (TN3-19.12) in established arthritis. Anti-CD4 treatment caused some reduction in paw-swelling but did not significantly prevent joint erosion. A suboptimal dose of anti-TNF alone had no significant effect on arthritis. In contrast, anti-CD4 plus suboptimal anti-TNF significantly reduced paw-swelling, limb involvement, and joint erosion. As previously reported, an optimal dose of anti-TNF alone inhibited paw-swelling, limb involvement, and joint erosion. However, optimal anti-TNF combined with anti-CD4 caused significantly greater reductions in paw-swelling and joint erosion than those achieved by optimal anti-TNF alone. Coadministration of anti-CD4 was also effective in preventing an antibody response to the hamster anti-TNF antibody, which may have implications for long-term therapy in human disease. Thus anti-CD4 acts synergistically with anti-TNF in ameliorating established collagen-induced arthritis and this combined therapeutic approach may provide effective long-term control of rheumatoid arthritis. |
| Authors | R O Williams, L J Mason, M Feldmann, R N Maini
(Affiliation: Kennedy Institute of Rheumatology, London, United Kingdom.)
|
| Journal | Proceedings of the National Academy of Sciences of the United States of America
(Proc Natl Acad Sci U S A)
Vol. 91
Issue 7
Pg. 2762-6
(Mar 29 1994)
ISSN: 0027-8424 UNITED STATES |
| PMID | 7908442
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Antibodies, Monoclonal
- Antigens, CD4
- Immunoglobulin G
- Immunoglobulin M
- Tumor Necrosis Factor-alpha
- Collagen
|
| Topics |
- Animals
- Antibodies, Monoclonal
(therapeutic use)
- Antigens, CD4
(immunology)
- Arthritis, Rheumatoid
(chemically induced, therapy)
- CD4-Positive T-Lymphocytes
(cytology)
- Collagen
(immunology, pharmacology)
- Drug Synergism
- Extremities
(pathology)
- Immunoglobulin G
(blood)
- Immunoglobulin M
(blood)
- Joints
(pathology)
- Male
- Mice
- Mice, Inbred DBA
- Time Factors
- Tumor Necrosis Factor-alpha
(immunology)
|
