PMID: 7536938Apr 11, 1995Paper

Prevention of autoimmune demyelination in non-human primates by a cAMP-specific phosphodiesterase inhibitor

Proceedings of the National Academy of Sciences of the United States of America
C P GenainS L Hauser

Abstract

Experimental allergic encephalomyelitis (EAE) is an autoimmune disease of the central nervous system that serves as a model for the human disease multiple sclerosis. We evaluated rolipram, a type IV phosphodiesterase inhibitor, for its efficacy in preventing EAE in the common marmoset Callithrix jacchus. In a blinded experimental design, clinical signs of EAE developed within 17 days of immunization with human white matter in two placebo-treated animals but in none of three monkeys that received rolipram (10 mg/kg s.c. every other day) beginning 1 week after immunization. In controls, signs of EAE were associated with development of cerebrospinal fluid pleocytosis and cerebral MRI abnormalities. In the treatment group, there was sustained protection from clinical EAE, transient cerebrospinal fluid pleocytosis in only one of three animals, no MRI abnormality, and marked reduction in histopathologic findings. Rolipram-treated and control animals equally developed circulating antibodies to myelin basic protein. Thus, inhibition of type IV phosphodiesterase, initiated after sensitization to central nervous system antigens, protected against autoimmune demyelinating disease.

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Citations

Nov 1, 1995·Annals of Neurology·S L Hauser
Jul 11, 1998·Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine·E T AhrensR E Jacobs
Feb 28, 1998·Immunologic Research·C S ConstantinescuA M Rostami
Dec 4, 2009·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Maria Vittoria SimoniniDouglas L Feinstein
Mar 17, 1999·European Journal of Pharmacology·M XiangF Nicoletti
Nov 1, 1996·Journal of the Neurological Sciences·C S ConstantinescuA Rostami
May 1, 1997·Trends in Pharmacological Sciences·M M TeixeiraP G Hellewell
May 29, 2000·Immunology Today·B A 't HartJ D Laman
Nov 14, 1997·Immunology Today·A EiglerS Endres
Aug 15, 2002·Neurochemistry International·Douglas L FeinsteinElena Galea
Dec 1, 1996·Current Opinion in Immunology·F M Brennan, M Feldmann
Mar 28, 1998·The Journal of Experimental Medicine·B M SegalE M Shevach
May 17, 2000·The Journal of Experimental Medicine·R M Ransohoff, C Trebst
Mar 31, 2000·Current Opinion in Pulmonary Medicine·M S Barnette, D C Underwood
Dec 1, 1999·Annals of the Rheumatic Diseases·C LockL Steinman

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