Basic science studies: Statins act as pleiotropic immune modulators and have been reported to improve clinical outcomes in murine models of multiple sclerosis. Since the pathological formation of sarcoid granulomas is driven in part by highly polarized T helper (Th)-1 immune responses to unidentified infectious or environmental antigens, we evaluated effects of atorvastatin and mevastatin on (1) the expression of co-stimulatory and activation molecules on blood monocyte-derived human dendritic cells (DC) obtained from normal volunteers (NV); (2) differentiation of human naive Th1 lymphocytes; and, (3) production of Th1 cytokines and chemokines in alveolar macrophages from patients with pulmonary sarcoidosis. Effects of statins on the expression, by immature DC, of co-stimulatory and activation molecules in response to E.coli LPS 0128:B12 were assessed by flow cytometry. Incubation of DC with 50 micro M atorvastatin or mevastatin, between days 4 and 6 of culture, reduced the LPS(1 micro g/mL)-induced expression of CD86, CD83, CD80, and HLA-DR. In naive T-lymphocytes, purified from human umbilical cord blood and cultured under Th1 conditions, 1 micro M atorvastatin reduced the expression of CXCR3+ CD4+ T-lymphocytes. In alveolar macrophages from sarcoid patients (not on immunosuppressive medications), 30 micro M atorvastatin significantly inhibited the production of IP-10, Mig, MCP-1, MIP-1alpha;, and MIP-1Beta. At 10 micro M, atorvastatin also inhibited the production of IP-10 and MCP-1. Thus, statins, by decreasing the expression of co-stimulatory and activation molecules on dendritic cells, and by suppressing T-cell differentiation and chemokine production in alveolar macrophages, might have beneficial effects in patients with sarcoidosis.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Intramural Research (Z01)
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Bladder and Prostatic Cancer Review Committee (BP)
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U.S. National Heart Lung and Blood Inst
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