title: IL-6R distribution in normal human and cynomolgus monkey tissues.
abstract: 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.
authors.affiliation: Safety Assessment Department, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan. katoath@chugai-pharm.co.jp
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Kato
authors.forename: Takeshi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Masaki
authors.initials: M
authors.lastname: Yamazaki
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Deki
authors.forename: Masami
authors.initials: M
authors.lastname: Suzuki
mesh_terms: 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
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015850:Interleukin-6; D015100:3,3'-Diaminobenzidine; C502936:tocilizumab