Blood Mononuclear Cell Mitochondrial Respiratory Chain Complex IV Activity is Decreased in Multiple Sclerosis Patients: Effects of β-Interferon Treatment

Objectives: Evidence of mitochondrial respiratory chain (MRC) dysfunction and oxidative stress has been implicated in the pathophysiology of multiple sclerosis (MS). However, at present, there is no reliable low invasive surrogate available to evaluate mitochondrial function in these patients. In view of the particular sensitivity of MRC complex IV to oxidative stress, the aim of this study was to assess blood mononuclear cell (BMNC) MRC complex IV activity in MS patients and compare these results to age matched controls and MS patients on beta-interferon treatment. Methods: Spectrophotometric enzyme assay was employed to measure MRC complex IV activity in blood mononuclear cell obtained multiple sclerosis patients and aged matched controls. Results: MRC Complex IV activity was found to be significantly decreased (p < 0.05) in MS patients (2.1 +/- 0.8 k/nmol x 10(-3); mean +/- SD] when compared to the controls (7.2 +/- 2.3 k/nmol x 10(-3)). Complex IV activity in MS patients on beta-interferon (4.9 +/- 1.5 k/nmol x 10(-3)) was not found to be significantly different from that of the controls. Conclusions: This study has indicated evidence of peripheral MRC complex IV deficiency in MS patients and has highlighted the potential utility of BMNCs as a potential means to evaluate mitochondrial function in this disorder. Furthermore, the reported improvement of complex IV activity may provide novel insights into the mode(s) of action of beta-interferon.