This project aims to elucidate immunological mechanisms underlying drug induced hypersensitivity. Further more this project intends to develop and improve strategies to predict the potential of drugs to induce hypersensitivity.

In vivo oral exposure sensitisation and popliteal lymph node assays are used to determine mechanisms of drug induced hypersensitivity and hepatotoxicity. Several cell biological and immunological methods are used for read out of relevant parameters, e.g. serum antibody levels, T and B cell responses.

Adverse drug reactions related to hepatotoxicity, blood dyscrasias and drug hypersensitivity are responsible for the top three of drug withdrawals due to toxicity. This research project aims to assess how pharmaceutical drugs that induce these adverse effects interfere with immunological processes at the interface between innate with adaptive immune responses. Focus will be on the activation of dendritic cells (by oxidative stress and apoptotic/necrotic cells), activation of NK cells, interference with costimulation, and disturbance of immunoregulation (regulatory T cells). These mechanisms will be studied in relation to systemic immunization to combinations of drugs with bystander antigens, and in relation to the immune system of the liver. Acquired knowledge will help to develop predictive preclinical test strategies for drug hypersensitivities.