Testing of immunomodulatory properties in vitro.

The immune response of different species to a given stimulus varies considerably. The in vitro evaluation of immunomodulatory properties of test compounds therefore prompts the use of human cells. We have conducted experiments on human whole blood incubations which offer the advantages of few preparation artefacts, natural cell environment and easy performance. Ten different immune stimuli were used to initiate leukocyte mediator release. Out of > 20 factors as readout, each and every stimulus released a unique set of factors with different kinetics and concentration dependences. We also used liver macrophages as an alternative cellular model. In this model, over-activation of the macrophages by endotoxin released a toxic combination of factors which killed co-cultured hepatocytes. Co-culture experiments were carried out with primary rat as well as with human liver cells to check for common mechanisms. Furthermore, we added human neutrophil granulocytes to these co-cultures which synergized with the macrophages in killing hepatocytes. Since a similar cellular interaction exists in vivo, this extended cell system bears additional characteristics of the in vivo situation. Therefore, these in vitro models of basic mechanisms of inflammation might be suitable for the evaluation of pro- and anti-inflammatory properties of test compounds.