Blockage of interleukin-6 receptor ameliorates joint disease in murine collagen-induced arthritis.
OBJECTIVE
To clarify the role of interleukin-6 (IL-6) in the pathogenesis of collagen-induced arthritis (CIA).


METHODS
CIA was induced by immunizing twice at a 3-week interval with bovine type II collagen (CII) emulsified with complete adjuvant. Rat anti-mouse IL-6 receptor (anti-IL-6R) monoclonal antibody MR16-1 or isotype-matched control antibody KH-5 was then injected once intraperitoneally. Symptoms of arthritis were evaluated with a visual scoring system, and serum anti-CII antibody and IL-6 levels were measured by enzyme-linked immunosorbent assay. In addition, the CII responsiveness of splenic lymphocytes from mice with CIA was examined.


RESULTS
In mice with CIA, excess production of IL-6 in sera was observed within 24 hours after the first CII immunization, and then rapidly decreased. Serum IL-6 increased again beginning 14 days after immunization, in conjunction with the onset of arthritis. When MR16-1 was injected immediately after immunization with CII, it inhibited the development of arthritis in a dose-dependent manner. Furthermore, MR16-1-treated mice exhibited lower serum levels of IgG anti-CII antibody and reduced responsiveness of lymphocytes to CII. This suppressive effect was observed when MR16-1 was injected on day 0 or 3, but not when injected on day 7 or 14.


CONCLUSIONS
IL-6 produced after CII immunization appears to play an essential role in the immunity to CII, and anti-IL-6R antibody reduces the development of CIA by suppressing IL-6 signal transduction.
Takagi
N
N
Chugai Pharmaceutical Company Ltd., Shizuoka, Japan.
Mihara
M
M
Moriya
Y
Y
Nishimoto
N
N
Yoshizaki
K
K
Kishimoto
T
T
Takeda
Y
Y
Ohsugi
Y
Y
D000818:Animals; D000906:Antibodies / Q000097:blood; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000139:chemically induced*; D003094:Collagen / Q000276:immunology; D004195:Disease Models, Animal; D015850:Interleukin-6 / Q000097:blood; D007592:Joint Diseases / Q000150:complications*; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors* / Q000276:immunology; D013154:Spleen / Q000166:cytology
D000906:Antibodies; D000911:Antibodies, Monoclonal; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D003094:Collagen