Clarifying controversy in multiple sclerosisMultiple sclerosis (MS) is a crippling autoimmune disease of the central nervous system (CNS) in which the protective nerve cell coating called myelin is damaged. Although uncontrolled CNS inflammation by immune cells called microglia (MG) and production of the protein TNF-alpha are considered important causes of demyelination and loss of nerve (neuron) function in MS, there is evidence to suggest that a controlled inflammatory response may actually restore damaged myelin and nerve function. Now, in a study appearing online on March 23 in advance of print publication in the April issue of the Journal of Clinical Investigation, researcher Michal Schwartz and colleagues at the Weizmann Institute of Science in Israel help clarify the controversy by reporting that it is the mechanism by which the MGs are activated that determines whether they are destructive or protective. Using both mouse and rat animal models of MS, the authors show that production by immune cells known as helper T cells of small amounts of a proinflammatory protein called IFN-gamma or production of an anti-inflammatory protein IL-4 could stimulate MGs to support nerve cell survival. In contrast, the researchers show that MGs fail to protect neurons when they are exposed to high doses of IFN-gamma, because high levels of IFN-gamma stimulate the MGs to produce TNF-alpha. The results demonstrate that the helper T cells can have direct control over MG action, stimulating them to either support or destroy nerve cell function through production of IL-4, and suggest that stimulation of MGs with IL-4 may help in MS clinical recovery.
TITLE: Induction and blockage of oligodendrogenesis by differently activated microglia in an animal model of multiple sclerosis
Weizmann Institute of Science, Rehovot, Israel
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Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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