In vivo blocking effects of a humanized antibody to human interleukin-6 receptor on interleukin-6 function in primates.
A humanized antibody to human interleukin-6 (IL-6) receptor, MRA, which was constructed by grafting the complementary determining regions, is expected to be useful as a therapeutic agent for IL-6-related diseases, especially multiple myeloma. We examined the ability of MRA to block the in vivo function of IL-6 and its serum concentration profile in primates. Cynomolgus monkeys were intravenously administered with MRA at doses of 0 (vehicle) or 5 mg/kg, then subcutaneously injected with human IL-6 at a dose of 5 micrograms/kg, once a day for 7 days. The injections of IL-6 increased blood platelet counts two-fold and elevated serum C-reactive protein levels to 0.15 to 0.17 mg/ml. These IL-6-induced typical responses were completely inhibited by single pretreatment with MRA. Serum concentrations of MRA were maintained for a long period; some even at one week after administration, were regarded as having sufficient levels to inhibit the myeloma cell growth. These findings suggest that MRA may be effective in the treatment of IL-6-related diseases.
Shinkura
H
H
Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co. Ltd., Shizuoka, Japan.
Imazeki
I
I
Yamazaki
M
M
Oda
Y
Y
Kotoh
M
M
Mihara
M
M
D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D002097:C-Reactive Protein / Q000032:analysis; D016466:CHO Cells; D006224:Cricetinae; D005260:Female; D006801:Humans; D008252:Macaca fascicularis; D008297:Male; D010976:Platelet Count; D019947:Receptors, Interleukin-6 / Q000276:immunology*; D011994:Recombinant Proteins / Q000494:pharmacology; D000093242:Interleukin-6 Inhibitors
D000906:Antibodies; D002097:C-Reactive Protein; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins; D000093242:Interleukin-6 Inhibitors