Anti-interleukin 6 (IL-6) receptor antibody suppresses Castleman's disease like symptoms emerged in IL-6 transgenic mice.
Transgenic mice carrying human IL-6 cDNA fused with a murine major histocompatibility class-I promoter (H-2L(d)) were serially administered with anti-interleukin-6 receptor (IL-6R) monoclonal antibody (mAb), MR16-1, from the age of 4 weeks to estimate its efficacy on a variety of disorders developed in these mice, most of which are similar to the disorders associated with Castleman's disease. In the control mice treated with isotype-matched mAb, a massive and multiple IgG1 plasmacytosis, mesangial proliferative glomerulonephritis, leukocytosis, thrombocytosis, anemia and abnormalities of blood chemical parameters have developed in accordance with the elevation of serum IL-6, and 50% of mice have died of renal failure by 18 weeks of age. In contrast, the treatment with MR16-1 prevented all these symptoms and prolonged the lifetime of the majority of the mice. Thus, the constitutive overexpression of IL-6 caused various disorders, and the treatment with anti-IL-6R mAb completely prevented from these symptoms. These results clearly confirm that IL-6 indeed plays an essential role in the pathogenesis of a variety of disorders. Furthermore, anti-IL-6R mAb could provide novel therapy for Castleman's disease and MR16-1 should be a useful tool to estimate therapeutic potential of IL-6 antagonists in a variety of murine models for human disease.
Katsume
Asao
A
Department of Medical Science I, School of Health and Sport Sciences, Osaka University, Osaka, Japan. katsumeaso@chugai-pharm.co.jp
Saito
Hiroyuki
H
Yamada
Yoshiki
Y
Yorozu
Keigo
K
Ueda
Otoya
O
Akamatsu
Ken-ichi
K
Nishimoto
Norihiro
N
Kishimoto
Tadamitsu
T
Yoshizaki
Kazuyuki
K
Ohsugi
Yoshiyuki
Y
D000818:Animals; D000906:Antibodies / Q000276:immunology* / Q000494:pharmacology; D005871:Castleman Disease / Q000188:drug therapy / Q000276:immunology*; D005921:Glomerulonephritis / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D007668:Kidney / Q000276:immunology / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D019947:Receptors, Interleukin-6 / Q000276:immunology*
D000906:Antibodies; D015850:Interleukin-6; D019947:Receptors, Interleukin-6