A cell line assay system for predicting the response of human blood to endotoxin.
Some parenteral drugs augment the in vivo action of endotoxin. It is necessary to regulate the overall toxic action of contaminating endotoxin by developing a clinically relevant test method for the safety control of such drugs. Although the responses of human peripheral blood cells (hPBC) to endotoxins to produce tumour necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), and IL-1beta showed considerable variation depending on the endotoxin and also on the individuals used as sources of blood, the responses to each of the endotoxins evaluated relative to that to the Japanese reference standard endotoxin were found to be highly reproducible irrespective of the sources of hPBC. The evaluation procedure based on the relative responsiveness to various endotoxins was shown to be highly effective to detect differences in responsiveness among the endotoxin test, the pyrogen test, and the cytokine induction in hPBC. When eight human monocytoid cell lines were examined, only THP-1 and 28SC cells showed a significant dose-dependent IL-6 production. However, THP-1 failed to show consistency with hPBC in responses to the panel of endotoxins. 28SC cells showed appropriate consistency with hPBC not only in terms of respective responses to the endotoxins but also with regard to detection of the effect of human interferons to augment endotoxin to induce IL-6.
Yamamoto
Akihiko
A
Department of Bacterial Pathogenesis and Infection Control, National Institute of Infectious Diseases, Tokyo 208-0011, Japan. yama-aki@nih.go.jp
Sakai
Takeo
T
Ochiai
Masaki
M
Kamachi
Kazunari
K
Kataoka
Michiyo
M
Toyoizumi
Hiromi
H
Horiuchi
Yoshinobu
Y
D000818:Animals; D001773:Blood Cells / Q000187:drug effects*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004731:Endotoxins / Q000633:toxicity*; D005260:Female; D005334:Fever / Q000139:chemically induced; D006801:Humans; D007372:Interferons / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis; D011817:Rabbits; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D004731:Endotoxins; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D007372:Interferons