NK-cell activity in immunotoxicity drug evaluation.
NK-cell activity as a tool for detection of immunotoxic effects of new human drugs has gained further attention when the recent European note for guidance CPMP/SWP/1042/99 was adopted. The inclusion of NK-cell activity plus distribution of lymphocyte subsets were suggested as an alternative to the primary antibody response to a T-cell dependent antigen. Either of the two test alternatives should be included as a routine parameter in at least one repeated dose-toxicity study, rats or mice being the species of choice. The standard procedure for measuring NK-cell activity is the 51Cr-release assay. However, a new flow-cytometric assay, adapted for rat peripheral blood, does not require dedicated groups of animals, offers the possibility of repeated testing, and shows at least as sensitive as the conventional 51Cr-release assay.
Cederbrant
Karin
K
Department of Molecular Toxicology/Immunotoxicology, Safety Assessment, AstraZeneca R&D Södertälje, SE-151 85, Södertälje, Sweden. karin.cederbrant@astrazeneca.com
Marcusson-Ståhl
Maritha
M
Condevaux
Fabienne
F
Descotes
Jacques
J
D000818:Animals; D004341:Drug Evaluation / Q000331:legislation & jurisprudence; D005434:Flow Cytometry; D017408:Guidelines as Topic; D006801:Humans; D000922:Immunotoxins / Q000633:toxicity*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology*; D010641:Phenotype; D014481:United States; D014486:United States Food and Drug Administration
D000922:Immunotoxins