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Sensitivity to Glucocorticoids Is Decreased in Relapsing Remitting Multiple Sclerosis

Departments of Neurology (L.M.L.v.W., C.H.P., B.M.J.U.), Molecular Cell Biology (D.F.R.M., C.D.D., T.K.v.d.B.), and Clinical Epidemiology and Biostatistics (B.M.J.U.), Vrije Universiteit Medical Center, 1007 MB Amsterdam, The Netherlands

Address all correspondence and requests for reprints to: L. van Winsen, Vrije Universiteit Medical Center, Department of Neurology, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. E-mail: l.vanwinsen2{at}vumc.nl.

Endogenous glucocorticoids (GC), which are under control of the hypothalamic-pituitary-adrenal axis, play an important role in controlling chronic inflammatory demyelinating diseases, like multiple sclerosis (MS). Increased hypothalamic-pituitary-adrenal axis activity has been found in MS patients and appeared to be negatively associated with acute inflammation. Exogenous GC are frequently used to treat relapses in MS, but the response to this treatment differs among patients, suggesting differences in sensitivity to GC. Previous, relatively small studies investigating GC sensitivity have yielded conflicting results. In the present study, we have investigated GC sensitivity in peripheral blood cells of MS patients (n = 117) and healthy controls (n = 45). GC sensitivity was measured by the in vitro suppressive effect of GC on lipopolysaccharide-stimulated TNF- production. Blood cells of MS patients, especially relapsing remitting MS patients, were less sensitive to GC compared with blood cells of healthy controls. This turned out to be unrelated to previous treatment with exogenous GC expressed as frequency of courses of iv steroids or interval since last course. The use of interferon ß was found to be associated with a lower GC sensitivity. However, after correction for the use of interferon ß, relapsing remitting MS patients remained less sensitive to GC.

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