| Abstract | We have evaluated the effects of anti-TNF-alpha, anti-IL-1, and combined anti-TNF-alpha/anti-CD4 therapy in collagen-induced arthritis. Blockade of TNF-alpha or IL-1 before disease onset delayed, but did not prevent, the induction of arthritis. When treatment was initiated after onset of arthritis, anti-TNF-alpha, anti-IL-1beta, and anti-IL-1R (which blocks IL-1alpha and IL-1beta) were all found to be effective in reducing the severity of arthritis, with anti-IL-1R and anti-IL-1beta showing greater efficacy than anti-TNF-alpha. Anti-IL-1beta was equally as effective as anti-IL-1R, indicating that IL-1beta plays a more prominent role than IL-1alpha in collagen-induced arthritis. An additive effect was observed between anti-TNF-alpha and anti-IL-1R in the prevention of joint erosion and in normalization of the levels of serum amyloid P. Combined anti-TNF-alpha/anti-CD4 therapy also caused normalization of serum amyloid P levels. The therapeutic effect of anti-TNF-alpha plus anti-CD4 was comparable to that of anti-TNF-alpha plus anti-IL-1R, suggesting that combined anti-TNF-alpha/anti-CD4 therapy prevents both TNF-alpha- and IL-1-mediated pathology. Anti-TNF-alpha treatment reduced IL-1beta expression in the joint and, conversely, anti-IL-1beta treatment reduced TNF-alpha expression. Combined anti-TNF-alpha/anti-CD4 treatment almost completely blocked the expression of IL-1beta, thereby confirming the ability of this form of combination therapy to prevent IL-1ss-mediated pathology. |
| Authors | R O Williams, L Marinova-Mutafchieva, M Feldmann, R N Maini
(Affiliation: Kennedy Institute of Rheumatology Division, Imperial College School of Medicine, London, United Kingdom. richard.o.williams at ic.ac.uk)
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| Journal | Journal of immunology (Baltimore, Md. : 1950)
(J Immunol)
Vol. 165
Issue 12
Pg. 7240-5
(Dec 15 2000)
ISSN: 0022-1767 UNITED STATES |
| PMID | 11120857
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Antibodies, Monoclonal
- Antigens, CD4
- Autoantibodies
- Immunoglobulin G
- Interleukin-1
- Receptors, Interleukin-1
- Tumor Necrosis Factor-alpha
- Collagen
|
| Topics |
- Acute-Phase Reaction
(immunology, metabolism, therapy)
- Animals
- Antibodies, Monoclonal
(administration & dosage, therapeutic use)
- Antigens, CD4
(immunology)
- Arthritis, Experimental
(immunology, metabolism, prevention & control)
- Autoantibodies
(biosynthesis, blood)
- Cattle
- Collagen
(immunology)
- Cricetinae
- Dose-Response Relationship, Immunologic
- Drug Therapy, Combination
- Immunization Schedule
- Immunoglobulin G
(biosynthesis, blood)
- Immunohistochemistry
- Injections, Intraperitoneal
- Interleukin-1
(antagonists & inhibitors, biosynthesis, immunology)
- Male
- Mice
- Mice, Inbred DBA
- Rats
- Receptors, Interleukin-1
(immunology)
- Tumor Necrosis Factor-alpha
(antagonists & inhibitors, biosynthesis, immunology)
|
