Trastuzumab-induced CCL20 and interleukin-8 mRNA in human whole blood ex vivo.
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.
Hasegawa
Setsuo
S
Sekino Clinical Pharmacology Clinic, Tokyo, Japan.
Kato
Hideaki
H
Yamaguchi
Hiroki
H
Yohda
Masafumi
M
Obara
Kazuhiko
K
Izutsu
Hiroshi
H
Ogura
Mieko
M
Mitsuhashi
Masato
M
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
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