arachidonyltrifluoromethane and Multiple-Sclerosis

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) that results in motor and sensory deficits. Although MS and its animal model, experimental autoimmune encephalomyelitis (EAE), are thought to be T cell-mediated diseases, the mechanisms underlying the lesions in the CNS are not fully understood. We propose that a strong candidate as a central mediator in evoking the complex pathological changes seen in MS and EAE is the enzyme cytosolic phospholipase A2 (cPLA2). One of the metabolic products of this enzyme is pro-inflammatory, while the other induces myelin breakdown, demyelination, and chemokine/cytokine expression. We provide evidence that cPLA2 is highly expressed in EAE lesions and show that blocking this enzyme leads to a remarkable reduction in the onset and progression of EAE.

Topics: Animals; Arachidonic Acids; Axons; Blotting, Western; CD4-Positive T-Lymphocytes; Cell Count; Chemokines; Cyclooxygenase 2; Cytokinins; Cytosol; Disease Models, Animal; Endothelial Cells; Enzyme Inhibitors; Female; Gene Expression; Immunohistochemistry; Inflammation; Isoenzymes; Macrophages; Mice; Mice, Inbred C57BL; Microscopy, Electron; Multiple Sclerosis; Oligonucleotide Array Sequence Analysis; Phospholipases A; Phospholipases A2; Prostaglandin-Endoperoxide Synthases; Random Allocation; Receptors, Chemokine; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Spinal Cord; Time Factors