title: Blockage of interleukin-6 receptor ameliorates joint disease in murine collagen-induced arthritis.
abstract: 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.
authors.affiliation: Chugai Pharmaceutical Company Ltd., Shizuoka, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Takagi
authors.forename: M
authors.initials: M
authors.lastname: Mihara
authors.forename: Y
authors.initials: Y
authors.lastname: Moriya
authors.forename: N
authors.initials: N
authors.lastname: Nishimoto
authors.forename: K
authors.initials: K
authors.lastname: Yoshizaki
authors.forename: T
authors.initials: T
authors.lastname: Kishimoto
authors.forename: Y
authors.initials: Y
authors.lastname: Takeda
authors.forename: Y
authors.initials: Y
authors.lastname: Ohsugi
mesh_terms: 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
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D003094:Collagen