Immunosuppressive Agents Enhance the Cytokine-lnduced Priming of Inflammatory Cells

The influence of the immunosuppressive substances cyclosporin A (CsA), FK506 and rapamycin on inflammatory mediators from cytokine-primed human leukocytes was studied. The cells were primed with granulocyte/macrophage-colony-stimulating factor, granulocyte-stimulating factor (G-CSF) and interleukin-3 (IL-3), and subsequently stimulated with the chemotactic peptide fMLP. The immunosuppressive agents CsA and FK506 enhanced the release of leukotriene B4 (LTB4) from human neutrophil granulocytes dependent on the priming with G-CSF and IL-3. IL-3-primed neutrophils released up to threefold higher amounts of LTB4 after subsequent stimulation with FK506 and fMLP. In contrast, the immunosuppressant rapamycin inhibited the formation of LTB4 after subsequent stimulation with fMLP. In addition to the well-documented inhibitory effects on lymphocyte function, our results indicate an enhancing effect of the immunosuppressive agents on the cellular inflammatory response of human peripheral blood neutrophils.