Inhibition of Interferon-beta Responses in Multiple Sclerosis Immune Cells Associated With High-Dose Statins

Figure 1. In vitro atorvastatin reduces interferon-beta effects. Mononuclear cells from 21 therapy-naive patients with relapsing-remitting multiple sclerosis were pretreated at 24 hours with 10-μM atorvastatin, then induced with 160 U/mL of interferon-beta-1b for 45 minutes (phosphorylated/activated STAT transcription factors) and 24 hours (downstream proteins, STAT1, STAT2, interferon regulatory factor 1 [IRF-1], and myxovirus resistance 1 [MxA]). Proteins were quantified with Western blots and normalized with actin. * P < .001 vs no-statin control, † P < .05. MEV indicates 100-μM mevalonate. Error bars indicate SEM.

Figure 2. Fourteen clinically stable patients with relapsing-remitting multiple sclerosis (RRMS) receiving interferon-beta plus statin therapy stopped interferon-beta therapy and stopped (A and C) or continued medium- or high-dose (B and D) statin therapy. Serum type 1 interferon activity and Western blots of STAT1 and STAT2 phosphorylation were performed at 0 and 4 hours after interferon-beta injection; in vivo–induced myxovirus resistance 1 and viperin proteins were measured with Western blots at 24 hours. MNCs indicates mononuclear cells.

Figure 3. Statins reduce interferon-beta therapy induction of serum type 1 interferon activity in 14 stable patients with relapsing-remitting multiple sclerosis. A, In vivo Rebif kinetics after a 3-day washout. B and C, Statin add-on therapy blocks interferon-beta therapy induction of serum interferon-α/β activity in 14 patients with relapsing-remitting multiple sclerosis. Serum samples were obtained at 8 AM after statin washout or long-term statin alone and then exactly 4 hours after interferon-beta injections or high-dose statins plus 4 hours of interferon-beta therapy. * P < .001 vs interferon alone (paired t test). Error bars indicate SEM.

Figure 4. Comparison of interferon and interferon with statin therapy. The addition of a statin blocks interferon-beta therapy induction of P-Y-STAT1 (A) and myxovirus resistance 1 (MxA) and viperin proteins (B) in 14 patients with relapsing-remitting multiple sclerosis. Mononuclear cell lysates from no drug, statin alone, interferon-beta alone at 4 hours, and 4 hours of interferon-beta plus statin conditions are shown. Proteins were quantified with Western blots and normalized with actin. * P < .001 vs interferon-beta (paired t test). Error bars indicate SEM.