Synergy between anti-CD4 and anti-tumor necrosis factor in the amelioration of established collagen-induced arthritis.
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.
Williams
R O
RO
Kennedy Institute of Rheumatology, London, United Kingdom.
Mason
L J
LJ
Feldmann
M
M
Maini
R N
RN
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000628:therapy*; D015704:CD4 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D003094:Collagen / Q000276:immunology / Q000494:pharmacology; D004357:Drug Synergism; D005121:Extremities / Q000473:pathology; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007596:Joints / Q000473:pathology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D014409:Tumor Necrosis Factor-alpha; D003094:Collagen