IL-6R distribution in normal human and cynomolgus monkey tissues.
Interleukin-6 (IL-6) is a pleiotropic cytokine and a contributing factor in many diseases such as rheumatoid arthritis, Castleman's disease, Crohn's disease, and multiple myeloma. Since the blockade of the signaling pathway of the IL-6/interleukin-6 receptor (IL-6R)/gp130 complex is considered to have therapeutic value in such diseases, we developed an IL-6R humanized antibody (tocilizumab). In the current report, distribution of IL-6R in both normal human and cynomolgus monkey tissues was assessed as fundamental data to support preclinical and clinical studies of tocilizumab. Human and cynomolgus monkey tissue panels were stained with commercially available anti-human IL-6R and a species- and isotype-matched negative antibody, as well as assay control slides. The detection system applied used an Envision immunoperoxidase staining procedure with DAB reaction. Positive reactions were observed in the tissue elements of lymphatic, hematopoietic, digestive, reproductive, exocrine, endocrine, neural, muscular, epidermal, respiratory, and urinary systems of the human and cynomolgus monkey tissue panels. The current report is inclusive of a wide variety of tissues and shows the distribution of IL-6R to be similar for both human and monkey tissues. We consider this information fundamental for the support and interpretation of preclinical and clinical studies of anti-IL-6R antibody therapy.
Kato
Atsuhiko
A
Safety Assessment Department, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan. katoath@chugai-pharm.co.jp
Watanabe
Takeshi
T
Yamazaki
Masaki
M
Deki
Toshiaki
T
Suzuki
Masami
M
D015100:3,3'-Diaminobenzidine; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques / Q000379:methods; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000378:metabolism*; D008252:Macaca fascicularis; D008297:Male; D015398:Signal Transduction / Q000187:drug effects; D013045:Species Specificity; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015850:Interleukin-6; D015100:3,3'-Diaminobenzidine; C502936:tocilizumab