Listed in Issue 236


WIPFLER and COLLEAGUES, (1)Department of Neurology, Christian-Doppler-Klinik, Paracelsus Medical University  and Salzburger Landeskliniken, Ignaz-Harrer-Strasse 79, 5020, Salzburg, Austria evaluated circadian rhythmicity of inflammatory serum parameters in multiple sclerosis (MS) biomarkers for activity and treatment response.


Inflammatory serum parameters are intensely investigated in the search of biomarkers for disease activity and treatment response in multiple sclerosis (MS). A reason for contradictory results might be the timing of blood collection for analyzing serum concentrations of inflammatory parameters which are subject to diurnal changes.


The authors included 34 untreated patients with relapsing-remitting MS and 34 age- and sex-matched healthy controls. 12 MS patients showed acute disease activity in corresponding MRI scans. Blood samples were obtained at 7.00, 11.00 am, 2.30, 6.00 and 9.30 pm within 1 day. The authors determined serum levels of cortisol and inflammatory markers including soluble tumor necrosis factor-beta (sTNF-β), soluble TNF-Receptor-1 (sTNF-R1) and -2 (sTNF-2), soluble vascular adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1) by ELISA.


The authors observed significantly higher serum levels of sTNF-R1 (p < 0.001) and sTNF-R2 (p < 0.001) in the morning and a significant decline of sICAM-1 (p < 0.005) and sVCAM-1 (p < 0.001) in the afternoon in both, MS patients and healthy controls. Comparison of diurnal serum levels between MS patients with active versus with non-active disease revealed significantly higher serum levels of sVCAM-1 (p < 0.05) around noon and in the early afternoon in MS patients with active disease. A significant decline of sICAM-1 (p < 0.05) in the afternoon was seen in MS patients with active and non-active disease.


Our data indicate that increased awareness of potential diurnal serum concentration changes of biomarkers can eliminate one major cause of biased data as they occur in most of the investigated immunological parameters.


Wipfler P(1), Heikkinen A, Harrer A, Pilz G, Kunz A, Golaszewski SM, Reuss R, Oschmann P, Kraus J. Circadian rhythmicity of inflammatory serum parameters: a neglected issue in the  search of biomarkers in multiple sclerosis.  J Neurol. 260(1):221-7. Jan 2013. doi: 10.1007/s00415-012-6622-3. Epub Aug 9 2012.


Very interesting, perhaps unexpected results of circadian rhythmicity of inflammatory serum parameters.

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