Phosphodiesterase type IV inhibitors in the treatment of multiple sclerosis.
Multiple sclerosis is an autoimmune disease with inflammatory lesions localized to the white matter of the central nervous system. Early on, the disease is characterized by episodes of exacerbations and remissions. During exacerbations there is an acute inflammatory infiltrate characterized by the presence of mononuclear cells, monocytes, and T lymphocytes. These cells produce proinflammatory cytokines that have been implicated in the amplification of the inflammatory response as well as in the damage of oligodendrocytes. The inflammation ultimately results in loss of myelin and oligodendrocyte cell death (demyelination). Thus therapies aimed at preventing the inflammatory response may have a beneficial effect on the course of the disease. One such therapy is treatment with inhibitors of phosphodiesterase type IV. These drugs have proven to be extremely effective in the prevention and treatment of experimental allergic encephalomyelitis, the animal model for multiple sclerosis. These experiments, as well as other data discussed here, provide a rationale for the treatment of multiple sclerosis with inhibitors of phosphodiesterase type IV.
Dinter
H
H
Department of Immunology, Berlex Biosciences, Richmond, CA 94804, USA.
Onuffer
J
J
Faulds
D
D
Perez
H D
HD
D000818:Animals; D000242:Cyclic AMP; D016207:Cytokines; D015870:Gene Expression; D006801:Humans; D008954:Models, Biological; D009103:Multiple Sclerosis / Q000188:drug therapy*; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology
D016207:Cytokines; D010726:Phosphodiesterase Inhibitors; D000242:Cyclic AMP