High levels of 15-oxygenated steroids in circulation of patients with multiple sclerosis: fact or fiction?

• Published in: Journal of lipid research 2011-01, Vol.52 (1), p.170-174
• Main Authors: Björkhem, I., Lövgren-Sandblom, A., Piehl, F., Khademi, M., Pettersson, H., Leoni, V., Olsson, T., Diczfalusy, U.
• Format: Article
• Language: English
• Subjects: 3β-hydroxy-5α-cholest-8-en-15-one; 5α-cholest-8ene-3β,15α-diol; Adult; autoxidation; Cholestenones - blood; Female; Humans; Hydroxycholesterols - blood; Male; Medicin och hälsovetenskap; Methods; Middle Aged; Multiple Sclerosis - blood; Oxidation-Reduction; Oxygen - metabolism; oxysterols
• ISSN: 0022-2275; 1539-7262; 1539-7262
• DOI: 10.1194/jlr.D011072

15-Oxygenated cholesterol species such as 5α-cholest-8(14)ene-3β,15α-diol (15HC) and 3β-hydroxy-5α-cholest-8(14)-en-15-one (15KC) are commercially available synthetic products unlikely to occur in biological systems. Surprisingly, Farez et al. recently reported that these two steroids occur in human circulation at levels considerably higher than those of any other endogenous oxysterol [Farez, M. et al. 2009. Toll-like receptor 2 and poly(ADP-ribose) polymerase 1 promote central nervous system neuroinflammation in progressive EAE. Nat. Immunol. 10: 958–964]. The levels were reported to be increased in patients with multiple sclerosis in a progressive phase and the authors suggested that this could be utilized diagnostically. Based on extensive in vitro experiments exposing cells to the same high levels of 15HC as found in vivo (1000 ng/ml) the authors concluded that 15HC may be an important pathogenetic factor in multiple sclerosis. Using combined gas chromatography-mass spectrometry we fail to detect significant plasma levels of 15HC either in healthy controls or in patients with multiple sclerosis (levels < 2 ng/ml). If 15KC is present in these plasma samples, the concentration of it must be