Cytokine signatures of human whole blood for monitoring immunosuppression

How to evaluate status of the immune system is extremely critical for clinical immunosuppressive treatment. In this study, we tested the secretion of cytokines in undiluted whole blood samples stimulated with Phorbol 12-myristate 13-acetate (PMA) and ionomycin (IONO), and compared the effects of dexamethasone (DEX), cyclosporine A (CsA) or mycophenolic acid (MPA), either alone or in combination, on cytokine profiles. The results showed that both DEX and CsA dose-dependently inhibited the production of eleven cytokines: interleukin (IL)-2, IL-4, IL-5, IL-6, IL-13, IL-17, interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF). Unexpectedly, MPA showed no obvious influences except for the mild inhibition on GM-CSF production. In combination treatment, cytokine profiles reflect not only the synergistic effects among drugs, but also the specific effect of the individual drug. Thus, the effects of different immunosuppressants could be reflected through their specific cytokine signatures, which can be applied to maximize immunosuppressive effects, while to minimize risk of infections and help physicians to reasonably apply immunosuppressants.