Differential cytokine and transcription factor expression in patients with allergic reactions to drugs

Allergic drug reactions (ADR) can be either immediate reaction (IR) (IgE mediated) or delayed reaction (DR) (T-cell mediated). They follow the Th1/Th2 paradigm, with DR expressing interferon-gamma (IFN-gamma) with down-regulation of interleukin-4 (IL-4) and IR expressing IL-4 with down-regulation of IFN-gamma. We studied the extension of this polarization in DR and IR by examining the cytokine and transcription factor profile in T-cell subpopulations during the acute phase of an ADR.

Expressions of cytokines [IL-4, IFN-gamma and tumor necrosis factor-alpha (TNF-alpha)] and transcription factors (c-maf, GATA-3 and T-bet) were analysed by semi-quantitative real time-polymerase chain reaction in peripheral blood mononuclear cells and in CD4 and CD8 subpopulations from ADR patients.

In DR, IFN-gamma, TNF-alpha and T-bet increased significantly in both CD4 and CD8 subpopulations, depending on the clinical severity. In IR, IL-4, c-Maf and GATA-3 were increased, but only significantly in CD4. A positive correlation existed between IFN-gamma and T-bet in DR and between IL-4 and c-Maf and GATA-3 in IR. In DR, IFN-gamma, TNF-alpha and T-bet were increased during the acute phase in CD4 and CD8. In IR, IL-4, c-Maf and GATA-3 were all increased in the acute phase, but only in CD4.

These results support the Th1/Th2 paradigm in ADR, confirming previous findings that include the expression in both CD4 and CD8 T cells, and extending the observation to the transcription factors involved in the polarization of the immune response. Monitoring the reactions in the cell populations implicated, could be an important tool for assessing the mechanisms involved in ADR.