Humanized antibody to human interleukin-6 receptor inhibits the development of collagen arthritis in cynomolgus monkeys.
In the present study, we demonstrated the anti-arthritic effect of humanized anti-human IL-6 receptor (IL-6R) antibody, MRA, in cynomolgus monkey. MRA can react with monkey IL-6R and block signal transduction of IL-6. Collagen-induced arthritis (CIA) was induced by twice immunizing with bovine type II collagen (CII) emulsified with complete adjuvant. MRA was intravenously injected once a week, from the day of the first collagen immunization, for 13 weeks. The symptoms of arthritis were evaluated using a visual scoring system and radiography. Inflammatory parameters (C-reactive protein (CRP), fibrinogen, and erythrocyte sedimentation rate (ESR) and concentrations of anti-CII antibody, anti-MRA antibody, and MRA were monitored regularly. At the end of the study, histological evaluation was carried out. MRA, at a dose of 10 mg/kg, gave rise to statistically significant suppression. The elevation of serum CRP and fibrinogen levels and ESR were also inhibited. Furthermore, radiographic and histological examination showed that MRA treatment suppressed joint destruction. Our results demonstrate that IL-6 plays an important role in monkey CIA and that MRA may be an attractive agent for the treatment of rheumatoid arthritis.
Mihara
M
M
Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co. Ltd., Shizuoka, Japan.
Kotoh
M
M
Nishimoto
N
N
Oda
Y
Y
Kumagai
E
E
Takagi
N
N
Tsunemi
K
K
Ohsugi
Y
Y
Kishimoto
T
T
Yoshizaki
K
K
Takeda
Y
Y
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D001168:Arthritis / Q000000981:diagnostic imaging / Q000473:pathology / Q000517:prevention & control*; D016466:CHO Cells; D002417:Cattle; D003094:Collagen / Q000276:immunology*; D006224:Cricetinae; D005260:Female; D006801:Humans; D007114:Immunization; D015850:Interleukin-6 / Q000502:physiology; D008252:Macaca fascicularis; D008297:Male; D011859:Radiography; D019947:Receptors, Interleukin-6 / Q000276:immunology*
D000906:Antibodies; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D003094:Collagen