Whole blood cytokine response as a measure of immunotoxicity

Immunotoxicity, although increasingly recognized as a potential hazard, sti ll lacks standardized in vivo and in vitro models. The considerable species differences and species-specific effects in immune responses prompt the de velopment of human in vitro test systems. Immunotoxic reactions comprise ac tivation (inflammatory processes, autoaggressive processes, pyrogenicity), sensitization (priming, idiosyncratic reactions) and impairment of immune r esponses (anergy, immunosuppression). We have previously studied a human wh ole blood system which allows the study of the release of inflammatory cyto kines in response to a variety of stimuli. This model allows the assessment of this basic immune mechanism without preparation artefacts and relativel y small interindividual variances. We have used this model previously to as sess pyrogens, namely type (1) immunotoxic reactions. The model also proved to be suitable for immunopharmacological studies in vitro as well as ex vi vo. Here, we studied the suitability of the test system to study type (3) i mmunotoxic effects. In order to also allow ex vivo studies, we have transfe rred the system to murine blood. This report summarizes our own use of this model with special emphasis on immunotoxicological studies. Our own listed bibliography gives access to the variety of applications of the human whol e blood model since its introduction in 1982. (C) 2001 Elsevier Science Ltd . All rights reserved.