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Published online before print December 30, 2005

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(Journal of Leukocyte Biology. 2006;79:529-538.)
© 2006 by Society for Leukocyte Biology

Differential effects of statins on relevant functions of human monocyte-derived dendritic cells

Atilla Yilmaz^*,1, Christine Reiss^*, Alexander Weng^*, Iwona Cicha^*, Christian Stumpf^*, Alexander Steinkasserer, Werner G. Daniel^* and Christoph D. Garlichs^*

^* Medical Clinic II and
Department of Dermatology, University of Erlangen-Nuremberg, Germany

¹ Correspondence: Medical Clinic II, University of Erlangen-Nuremberg, Ulmenweg 18, 91054 Erlangen, Germany. E-mail: A.Yilmaz.med2.uni-erlangen{at}email.de

Statins were shown to possess immunomodulating properties, but the mechanisms of statin effects on the immune system are poorly understood. We analyzed the influence of statins on professional antigen-presenting dendritic cells (DC). Immature DC were cultivated from monocytes of healthy donors. DC maturation was induced by lipopolysaccharide (LPS; 1 µg/mL). Unstimulated and LPS-stimulated DC were treated with simvastatin or atorvastatin (0.1–1 µM). The expression of CD40, CD83, CD86, and human leukocyte antigen-DR on unstimulated and LPS-stimulated DC was reduced significantly by statins, and the expression of Toll-like receptor 2 (TLR2) and TLR4 on LPS-stimulated DC was enhanced temporarily. Statins caused a significant reduction of endocytosis of fluorescein isothiocyanate-dextran by DC. Statins significantly inhibited the basal secretion of interleukin (IL)-6, IL-8, IL-12, and tumor necrosis factor from unstimulated DC, and their release from LPS-stimulated DC was enhanced. In mixed leukocyte reaction, preincubation of LPS-stimulated DC with statins significantly suppressed their clustering with T cells and their ability to induce T cell proliferation, CD71, and CD25 up-regulation on T cells and the secretion of interferon- and IL-2 from T cells. In conclusion, this study showed that statins suppressed endocytosis, basal secretion of proinflammatory cytokines, and the ability of DC to induce T cell proliferation, activation, and T helper cell type 1 differentiation. However, statin preincubation of LPS-stimulated DC caused a further increase in their secretion of proinflammatory cytokines.

Key Words: atherosclerosis • inflammation • immunity

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