Interferon-Beta Reduces Mitochondrial Distress in EAE

Background: Inflammatory tissue injury is the hallmark of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). This damage includes neuronal loss and recent observations suggest that oxidative stress and mitochondrial dysfunction play an important role in neuronal injury. Mitochondria are dynamic organelles that respond to oxidative stress by undergoing fission and fusion.  Interferon-beta (IFN-β) is a pleotropic cytokine which is widely used in the treatment of MS and is thought to act as an immunomodulator. Some evidence supports the ability of IFN-β treatment to reduce neuronal loss in MS but little is known about the mechanisms that might underlie this effect.

Objectives: The aim of this study was to examine the effect of IFN-β on mitochondrial dysfunction in myelin oligodendroglial peptide-induced EAE in C57Bl/6J mice.

Methods: EAE was induced with MOG peptide 35-55, genetically engineered bone marrow stem cells were used to deliver IFN-β and tissues were examined immunohistochemically as previously described (Makar, et al, J Neurol Sci 2008; 196: 67).

Results: We showed for the first time that the mitochondrial fission protein Fis1, is increased and the mitochondrial fusion protein, Mrf2, is decreased in this EAE model. This correlated with increases in Cytochrome C. EAE mice transplanted with the IFN-β producing cells had reduced Fis1 and increased Mrf2 toward normal levels and reduced Cytochrome C levels.

Conclusions: These results are consistent with increased mitochondrial distress in EAE and an IFN-β related reduction in distress. Further studies will be needed to determine whether IFN-β has a direct effect on mitochondria or the effect is secondary to a reduction in inflammation.