IMMUNOSUPPRESSIVE AGENTS ENHANCE THE CYTOKINE-INDUCED PRIMING OF INFLAMMATORY CELLS

The influence of the immunosuppressive substances cyclosporin A (CsA), FK506 and rapamycin on inflammatory mediators from cytokine-primed hu man leukocytes was studied. The cells were primed with granulocyte/mac rophage-colony-stimulating factor, granulocyte-stimulating factor (G-C SF) and interleukin-3 (IL-3), and subsequently stimulated with the che motactic peptide fMLP. The immunosuppressive agents CsA and FK506 enha nced the release of leukotriene B-4 (LTB(4)) from human neutrophil gra nulocytes dependent on the priming with G-CSF and IL-3. IL-3-primed ne utrophils released up to threefold higher amounts of LTB(4) after subs equent stimulation with FK506 and fMLP. In contrast, the immunosuppres sant rapamycin inhibited the formation of LTB(4) after subsequent stim ulation with fMLP. In addition to the well-documented inhibitory effec ts on lymphocyte function, our results indicate an enhancing effect of the immunosuppressive agents on the cellular inflammatory response of human peripheral blood neutrophils.