title: Trastuzumab-induced CCL20 and interleukin-8 mRNA in human whole blood ex vivo.
abstract: Heparinized human whole blood from 16 adult volunteers was stimulated with achievable blood concentrations of trastuzumab and rituximab at 37 degrees C for 4 h, then CCL20, IL8, and beta-actin mRNA were quantified. The fold increase of beta-actin was all less than 1.5, and heat aggregated IgG induced both IL8 and CCL20 mRNA in all cases, suggesting that the assay was performed appropriately. Rituximab reduced the levels of CCL20 mRNA in approximately 1/3 of subjects, whereas 50 μg/ml trastuzumab induced IL8 and CCL20 mRNA in more than half of subjects. Although the results do not directly indicate the toxicity of antibody medicines, the individual variation found under physiological ex vivo condition will be an interesting clinical research model for drug safety analysis.
authors.affiliation: Sekino Clinical Pharmacology Clinic, Tokyo, Japan.
authors.forename: Setsuo
authors.initials: S
authors.lastname: Hasegawa
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kato
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: Masafumi
authors.initials: M
authors.lastname: Yohda
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Obara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Izutsu
authors.forename: Mieko
authors.initials: M
authors.lastname: Ogura
authors.forename: Masato
authors.initials: M
authors.lastname: Mitsuhashi
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D054418:Chemokine CCL20 / Q000235:genetics*; D002850:Chromatography, Gel; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics*; D012333:RNA, Messenger / Q000097:blood* / Q000235:genetics; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C108355:CCL20 protein, human; C508606:CXCL8 protein, human; D054418:Chemokine CCL20; D007074:Immunoglobulin G; D016209:Interleukin-8; D012333:RNA, Messenger; D000068878:Trastuzumab