Suppressive effect of glucocorticoids on TNF-alpha production is associated with their clinical effect in multiple sclerosis.

A reduced sensitivity to glucocorticoids can affect the clinical effect of treatment with high-dose intravenous methylprednisolone in multiple sclerosis. We prospectively studied 27 multiple sclerosis patients who were treated with intravenous methylprednisolone. Before and after treatment in vitro stimulated TNF-alpha production in blood cells and the effect of in vitro administered glucocorticoids were determined as a measure of glucocorticoid sensitivity.

Outcome measurement in multiple sclerosis: detection of clinically relevant improvement.

Because the development of new treatments in multiple sclerosis as well as the awareness of the importance of patient-oriented measures have become more important in the last two decades, new outcome measures have been developed with the aim of being more responsive to change and more clinically relevant to patients. The ability to detect improvement is sparsely studied. In the present study we evaluate the responsiveness of the Expanded Disability Status Scale and two quantitative tests (the timed 25-foot walk test and the nine-hole peg test) separately and in combination, to detect improvement after intravenous methylprednisolone.

A glucocorticoid receptor gene haplotype (TthIII1/ER22/23EK/9beta) is associated with a more aggressive disease course in multiple sclerosis.

Context: In patients with multiple sclerosis (MS), glucocorticoids (GCs) might not be sufficiently able to restrain the immune system, possibly due to decreased GC sensitivity. This may be, at least partially, genetically determined. Previously, we reported a more aggressive disease course in patients with the glucocorticoid receptor (GR) gene ER22/23EK polymorphism, which has been shown to decrease GC sensitivity.

Proteolytic shedding of the macrophage scavenger receptor CD163 in multiple sclerosis.

The scavenger receptor CD163 is selectively expressed on tissue macrophages and human monocytes. CD163 has been implicated to play a role in the clearance of hemoglobin and in the regulation of cytokine production by macrophages. Membrane CD163 can be cleaved by matrix metalloproteinases (MMP) resulting in soluble CD163 (sCD163).

Sensitivity to glucocorticoids is decreased in relapsing remitting multiple sclerosis.

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.