Therapeutic potential of phosphodiesterase type 4 inhibition in chronic autoimmune demyelinating disease

N. Sommer, R. Martin, H. F. McFarland, L. Quigley, B. Cannella, C. S. Raine, D. E. Scott, P. A. Löschmann, M. K. Racke

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63 Scopus citations

Abstract

It was recently demonstrated that selective phosphodiesterase type 4 (PDE4) inhibition suppresses the clinical manifestations of acute experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), and inhibits the production of tumor necrosis factor-α (TNF- α), a pathogenetically central cytokine. Since the most common presentation of MS in humans is a relapsing-remitting course, we investigated the therapeutic potential of PDE4 inhibition in the relapsing-remitting EAE model of the SJL mouse. Administration of rolipram, the prototypic PDE4 inhibitor, reduced the clinical signs of EAE during both the initial episode of disease and subsequent relapses. In parallel, there was marked reduction of demyelination and also less inflammation throughout the central nervous system (CNS) of rolipram-treated animals. Gene expression of proinflammatory cytokines in the CNS was reduced in most of the rolipram-treated animals. Additional experiments demonstrated that PDE4 inhibition acted principally by inhibiting the secretion of Th1 cytokines, however, the encephalitogenic potential of myelin basic protein-specific T cells was not impaired. Our findings suggest that PDE4 inhibitors are a promising cytokine-directed therapy in chronic demyelinating disease.

Original languageEnglish (US)
Pages (from-to)54-61
Number of pages8
JournalJournal of Neuroimmunology
Volume79
Issue number1
DOIs
StatePublished - Oct 1 1997

Keywords

  • Cytokine
  • Experimental autoimmune encephalomyelitis
  • Multiple sclerosis
  • Phosphodiesterase type 4
  • Rolipram
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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    Sommer, N., Martin, R., McFarland, H. F., Quigley, L., Cannella, B., Raine, C. S., Scott, D. E., Löschmann, P. A., & Racke, M. K. (1997). Therapeutic potential of phosphodiesterase type 4 inhibition in chronic autoimmune demyelinating disease. Journal of Neuroimmunology, 79(1), 54-61. https://doi.org/10.1016/S0165-5728(97)00111-2