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Interferon-ß regulates cytokines and BDNF: greater effect in relapsing than in progressive multiple sclerosis

Department of Neurology, Gülhane Military Medical Academy, Etlik, Ankara 06018, Turkey, Department of Neurology, MC-2030, The University of Chicago, Chicago, IL 60637-1470, USA

AT Reder

Department of Neurology, MC-2030, The University of Chicago, Chicago, IL 60637-1470, USA, areder{at}neurology.bsd.uchicago.edu

The mechanism of action of interferon (IFN)-ß therapy in multiple sclerosis (MS) is only partially known, and its efficacy changes with disease stage. In different forms of MS, we determined how IFN-ß regulates mononuclear cell production of the important anti-inflammatory Th2 cytokine - IL-10, the Th1 cytokine - IFN-, and the brain-derived neurotrophic protein - BDNF. Activated T cells and monocytes from therapy-naïve patients secreted more IL-10 than healthy controls. During IFN-ß therapy, however, T cells produced less IL-10. In vitro, IFN-ß stimulated IL-10 production by activated T cells, but inhibited IL-10 secretion by activated monocytes, a richer source of IL-10 than T cells. The form of MS also affected cytokine production. IL-10 and BDNF levels in MNC were high during relapsing/remitting (RR) MS, but low in progressive MS. Surprisingly, IFN-ß therapy increased BDNF levels in antidepressant-naïve patients, but BDNF was lower during concurrent antidepressant drug therapy, suggesting an interaction between MS, depression, and neurodegeneration. IFN-ß in vitro strongly induced IL-10 and IFN- in activated T cells in RRMS, but not in progressive MS, suggesting IFN resistance. IFN-ß effects are specific for disease state and immune subsets, possibly explaining why IFN-ß therapy is most effective in early T cell-regulated RRMS, but less beneficial in progressive MS, where chronic plaques contain few T cells and high numbers of monocytes. Multiple Sclerosis 2007; 13: 459-470. http://msj.sagepub.com

Key Words: antidepressant drugs • BDNF • IL-10 • interferon-beta • interferon-gamma • multiple sclerosis

This version was published on May 1, 2007

Multiple Sclerosis, Vol. 13, No. 4, 459-470 (2007)
DOI: 10.1177/1352458506069672


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