Tocilizumab, a humanized anti-interleukin-6 receptor antibody, ameliorates joint swelling in established monkey collagen-induced arthritis

Biol Pharm Bull. 2008 Jun;31(6):1159-63. doi: 10.1248/bpb.31.1159.


We examined if tocilizumab, humanized anti-interleukin-6 receptor (IL-6R) antibody, can ameliorate joint swelling after the onset of arthritis in collagen-induced arthritis (CIA). CIA was induced by the immunization of bovine type II collagen in female cynomolgus monkeys. Tocilizumab (30 mg/kg) was administered weekly for 4 weeks after the onset of arthritis. Swelling of 16 proximal interphalangeal (PIP) joints of hands and feet was monitored by measuring the longitudinal and transverse axes of PIP joints and the oval area of each PIP was calculated. Serum was collected once a week after tocilizumab injection and blood chemistry, IL-6, soluble IL-6R (sIL-6R), and anti-tocilizumab antibody were measured. At the end of study, histopathological examination of joints was performed. Tocilizumab clearly reduced joint swelling in all animals without anti-tocilizumab antibody. Histopathological study showed significant decrease in the infiltration of neutrophils into inflamed joints was observed in tocilizumab-treated animals. In conclusion, tocilizumab improved established arthritis in monkey and monkey CIA model is useful for the analysis of anti-arthritic effect of tocilizumab.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal*
  • Antibodies / blood
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal, Humanized
  • Arthritis, Experimental / chemically induced
  • Arthritis, Experimental / drug therapy*
  • Arthritis, Experimental / pathology
  • Biomarkers
  • C-Reactive Protein / biosynthesis
  • Collagen Type II*
  • Edema / pathology
  • Edema / prevention & control
  • Female
  • Foot / pathology
  • Hand / pathology
  • Interleukin-6 / blood
  • Joints / pathology
  • Macaca fascicularis
  • Neutrophil Infiltration / drug effects
  • Receptors, Interleukin-6 / antagonists & inhibitors*
  • Receptors, Interleukin-6 / immunology*


  • Anti-Inflammatory Agents, Non-Steroidal
  • Antibodies
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Biomarkers
  • Collagen Type II
  • Interleukin-6
  • Receptors, Interleukin-6
  • C-Reactive Protein
  • tocilizumab