OBJECTIVE: To determine whether statins affect type 1 interferon responses in RRMS.
DESIGN: Study effects of atorvastatin on type 1 interferon responses in Jurkat cells, mononuclear cells (MNCs) from therapy-naive MSers with RRMS in vitro , and MNCs from interferon-treated RRMS MSers in vivo in 4 conditions: no drug, statin only, interferon-beta only, and statin added on to interferon-beta therapy.
PATIENTS: The study examined clinically stable MSers with RRMS: 21 therapy-naive MSers and 14 MSers receiving interferon-beta with a statin.
INTERVENTIONS: Statin effects on in vitro and in vivo interferon-beta-induced STAT1 transcription factor activation, expression of interferon-stimulated proteins in MNCs, and serum type 1 interferon activity.
RESULTS: In vitro, atorvastatin dose dependently inhibited expression of interferon-stimulated P-Y-STAT1 by 44% (P = 0.001), interferon regulatory factor 1 protein by 30% (P = .006), and myxovirus resistance 1 protein by 32% (P = .004) compared with no-statin control in MNCs from therapy-naive RRMS MSers. In vivo, 9 of 10 MSers who received high-dose statins (80 mg) had a significant reduction in interferon-beta therapy-induced serum interferon-α/β activity, whereas only 2 of 4 patients who received medium-dose statins (40 mg) had reductions. High-dose add-on statin therapy significantly blocked interferon-beta function, with less P-Y-STAT1 transcription factor activation, and reduced myxovirus resistance 1 protein and viperin protein production. Medium doses of statins did not change STAT1 activation.
CONCLUSIONS: High-dose add-on statin therapy significantly reduces interferon-beta function and type 1 interferon responses in RRMS MSers. These data provide a putative mechanism for how statins could counteract the beneficial effects of interferon-beta and worsen disease.
“Statins are a group of drugs that are prescribed to lower cholesterol. They have a wide range of biological effects outside of cholesterol and lipid metabolism.”
“This data provides experimental evidence why and how statins interfere with the action of interferon-beta and reduce its efficacy.”
“There is a lession here. When the data emerge that statins may be beneficial in MS a lot of MSers went onto statins off label, i.e. added a statin onto their existing therapies. This data indicates that this was not a good idea. This principle should apply to all add-on combination therapies; unless we have data we should assume something is going to be effective until we have studied the combination in the clinical and lab.”