The influence of the proinflammatory cytokine, osteopontin, on autoimmune demyelinating disease

Multiple sclerosis is a demyelinating disease, characterized by inflammatio n in the brain and spinal cord, possibly due to autoimmunity. Large-scale s equencing of cDNA libraries, derived from plaques dissected from brains of patients with multiple sclerosis (MS), indicated an abundance of transcript s for osteopontin (OPN). Microarray analysis of spinal cords from rats para lyzed by experimental autoimmune encephalomyelitis (EAE), a model of MS, al so revealed increased OPN transcripts. Osteopontin-deficient mice were resi stant to progressive EAE and had frequent remissions, and myelin-reactive T cells in OPN-/- mice produced more interleukin 10 and less interferon-gamm a than in OPN+/+ mice. Osteopontin thus appears to regulate T helper cell-1 (T(H)1)-mediated demyelinating disease, and it may offer a potential targe t in blocking development of progressive MS.