Compared effects of morphine and nickel chloride on NK cell activity in vitro in rats and monkeys.
The measurement of natural killer (NK) cell activity often is recommended as an endpoint for inclusion in the non-clinical immunotoxicity evaluation of environmental chemicals and pharmaceuticals. To date, most data on the impact of immunotoxicants on NK cell activity have been obtained in the rat. Because non-human primates often are used in the safety evaluation of new medicinal products, there is a need to compare chemically induced changes in NK cell activity between rats and primates. In this study, the in vitro effects of nickel chloride and morphine hydrochloride were investigated on NK cell activity in the rat and the cynomolgus monkey. Despite some species-specific differences in the techniques used, rather similar results were obtained in the two species. At the higher concentration, nickel chloride induced a significant decrease in NK cell activity in the ranges of 21.6-24.3% (rat) and 34.4-42.2% (monkey), depending on the effector-to-target cell ratio used, and morphine hydrochloride induced a decrease in the ranges of 23.7-34.7% (rat) and 59.1-68.0% (monkey). These results suggest that NK cell activity can be used as a reliable endpoint for the assessment of immune effects during safety evaluation studies in the cynomolgus monkey.
Condevaux
F
F
MDS Pharma Services, BP 118, 69593 l'Arbresle Cedex, France.
Guichard
J
J
Forichon
A
A
Aujoulat
M
M
Descotes
J
J
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002857:Chromium / Q000378:metabolism; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008252:Macaca fascicularis; D008297:Male; D009020:Morphine / Q000633:toxicity*; D009532:Nickel / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D013154:Spleen / Q000166:cytology / Q000187:drug effects
D002857:Chromium; C022838:nickel chloride; D009020:Morphine; D009532:Nickel