Diagnosis of drug hypersensitivity: lymphocyte transformation test and cytokines

For all types of allergic reactions including immediate type of reactions, types II and III reactions as well as delayed-type reactions the recognition of the antigen by specifically sensitized T-lymphocytes is a prerequisite. Evidences for the key role of T-lymphocytes in the pathophysiology of allergic drug reactions are positive patch test reactions and the LTT. The proliferative response that can be measured by means of the incorporation of 3H-thymidine during DNA synthesis can be expressed as stimulation index (SI) which is the relation between the cell proliferation with antigen compared without antigen. In addition drug-specific activation of PBMC consistently resulted in IL-5 expression and secretion. The sensitivity of the LTT for the detection of drug sensitization could be improved up to 92% by the measurement of released interleukin-5. The expression and secretion of other cytokines such as IFN-gamma and IL-10 was less consistently and had a diagnostic sensitivity of 36 and 50%, respectively. Microarrays are a promising new technical platform to look for better markers which can be used as a read out in the LTT and other similar assays and to study pharmacological interactions between drugs including cytokines such as interferons and the immune system.