Immunotoxicological investigation using pharmaceutical drugs. In vitro evaluation of immune effects using rodent or human immune cells

Human lymphocyte activation assay: Anin vitromethod for predictive immunotoxicity testing

“…The assay should be relatively simple to perform, require small quantities of test article, use human cells, and allow moderate to high throughput. The need for a human cell-based assay is highlighted by in vitro assays where species differences in sensitivity to immunosuppressive compounds have been observed (Lang et al, 1993;Lebrec et al, 1995;Carfi et al, 2007). Above all, the method should be adequately sensitive to known immunosuppressive drugs.…”

“…For example, Barten et al (2003) demonstrated, using concanavalin A (ConA) stimulation in human whole blood assays, that rapamycin was more potent than cyclosporine, which was more potent than MPA. In addition, dexamethasone is more potent than cyclosporine at inhibiting proliferation of human PBMC when stimulated with ConA (Lebrec et al, 1995). Studies evaluating human CD8 + T-lymphocytes stimulated with anti-CD3 antibodies demonstrated that the response was more sensitive to inhibition by rapamycin than to cyclosporine (Combates et al, 1995).…”

Present and future ofin vitroimmunotoxicology in drug development

“…The proportion or absolute numbers of NK cells are modified after in vivo exposure to a consistent number of the substances and physical agents tested (Burns et al, 1994;Ross et al, 1996;Marcusson-Ståhl and Cederbrant, 2003). The predictive potential of such assays after in vitro exposure has been the subject of intensive investigation (Lebrec et al, 1995;Condevaux et al, 2001). The main limitation of the use of NK cell activity for in vitro studies is the rapidly loss of cell viability and of cytolytic function once cells are isolated (Hébert and Pruett, 2001).…”

Dose–Response Relationships of Weight, Cellularity, Plaque-Forming Cell Response, and Histology in the Spleen of Rats Treated with Antimetabolites

“…However, we do not deny the usefulness of immunofunctional assays to evaluate immunotoxicity, because there are many procedures (Vos and van Loveren, 1987;Luster et al, 1988;Verdier, 1992) and techniques (Miller, 1992;Fautz and Miltenburger, 1993;Crevel et al, 1994;Meredith and Miller, 1994;Lebrec et al, 1995) other than the PFC assay, including host resistance assays (Luster et al, 1993), which can provide valuable information about the possible mechanisms involved in chemical-induced immune dysfunction and the ability to resist infection and cancer.…”