FK506 suppresses neutrophil chemoattractant production by peripheral bloodmononuclear cells

To understand the mechanism of action of FK506 (Tacrolimus) on neutrophil c hemotaxis, we examined its effect on human neutrophil chemotaxis and neutro phil chemoattractant production by peripheral blood mononuclear cells. FK50 6 and cyclosporin A had no direct suppressive effect on neutrophil chemotax is induced by interleukin-8, leukotriene B-4, complement 5a (C5a), zymosan- activated serum and formyl-Met-Leu-Phe (fMLP). FK506 and cyclosporin A only slightly suppressed the chemotactic activity of platelet-activating factor (PAF). Dexamethasone did not inhibit the chemotactic activity of any chemo attractant. The supernatant of peripheral blood mononuclear cells stimulate d with anti-CD3 and CD2 antibodies induced neutrophil chemotaxis. FK506 and cyclosporin A suppressed the chemotactic activity of the supernatant in pa rallel to the suppression of interleukin-8 production by peripheral blood m ononuclear cells. Anti-interleukin-8 antibody completely suppressed the che motactic activity of the supernatant without drugs. These studies indicate that FK506 may exert a beneficial effect on human inflammatory diseases by suppressing neutrophil chemotaxis secondary to inhibition of chemoattractan t (for example, interleukin-8) production by leukocytes. (C) 2000 Elsevier Science B.V. All rights reserved.