Immunomodulatory synergy by combination of atorvastatin and glatiramer acetate in treatment of CNS autoimmunity
J. Clin. Invest. Olaf Stüve, et al. 116:1037 doi:10.1172/JCI25805 [
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Figure 5Combination therapy of atorvastatin and GA reduces secretion of proinflammatory cytokines and promotes secretion of IL-10 by monocytes. Bone marrow–derived monocytes/macrophages were isolated from (PL/J × SJL/J)F
1 mice as described in Methods. Treatment of monocytes with optimal doses of atorvastatin (10 μM) or GA (50 μM) suppressed secretion of proinflammatory cytokines IL-12 and TNF-α and promoted secretion of the antiinflammatory cytokine IL-10. Suboptimal doses of atorvastatin (0.1 μM) or GA alone (6.25 μM) did not alter cytokine secretion, whereas treatment using the combination of these suboptimal doses suppressed secretion of TNF-α and IL-12 and promoted IL-10 secretion. Monocytes in each group were pretreated with IFN-γ for 24 hours. Cytokine secretion by unstimulated monocytes was measured and recorded: IL-12, 112 (± 2); TNF-α, 153 (± 2); and IL-10, 141 (± 3) pg/ml. Treatment groups were compared to the control group (untreated) using 1-way ANOVA. Data are representative of 3 separate experiments. *
P < 0.05.