Whole blood cytokine response as a measure of immunotoxicity

Immunotoxicity, although increasingly recognized as a potential hazard, still lacks standardized in vivo and in vitro models. The considerable species differences and species-specific effects in immune responses prompt the development of human in vitro test systems. Immunotoxic reactions comprise activation (inflammatory processes, autoaggressive processes, pyrogenicity), sensitization (priming, idiosyncratic reactions) and impairment of immune responses (anergy, immunosuppression). We have previously studied a human whole blood system which allows the study of the release of inflammatory cytokines in response to a variety of stimuli. This model allows the assessment of this basic immune mechanism without preparation artefacts and relatively small interindividual variances. We have used this model previously to assess pyrogens, namely type (1) immunotoxic reactions. The model also proved to be suitable for immunopharmacological studies in vitro as well as ex vivo. Here, we studied the suitability of the test system to study type (3) immunotoxic effects. In order to also allow ex vivo studies, we have transferred 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 whole blood model since its introduction in 1982.