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  • Title: Protective effect of Rolipram in experimental autoimmune neuritis: protection is associated with down-regulation of IFN-gamma and inflammatory chemokines as well as up-regulation of IL-4 in peripheral nervous system.
    Author: Abbas N, Zou LP, Pelidou SH, Winblad B, Zhu J.
    Journal: Autoimmunity; 2000 Sep; 32(2):93-9. PubMed ID: 11078155.
    Abstract:
    Rolipram, a phosphodiesterase type 4 inhibitor, is reported to have anti-inflammatory effects. It can markedly downregulate antigen-driven T cell proliferation and suppress TNF-(alpha and TNF-beta production in vitro and in vivo, which have led to its use in the treatment of a number of autoimmune disorders including experimental autoimmune encephalomyelitis (EAE) and experimental autoimmune neuritis (EAN). EAN is a CD4+ T cell-mediated demyelinating autoimmune disease of peripheral nervous system (PNS) that represents an animal model for the study of the immunopathogenesis and immunotherapy of Guillain-Barré syndrome (GBS) in human. In the previous study, we reported that suppression of EAN by Rolipram was associated with down-regulated myelin antigen-induced T cell responses as well as downregulated IFN-gamma and TNF-alpha production. Here we report that EAN induced in Lewis rats by inoculation with the PNS P2 protein peptide 57-81 and Freund's complete adjuvant (FCA), was strongly suppressed by Rolipram administered twice daily intraperitoneally from day 9 post immunization (p.i.), i.e. after onset of clinical EAN to day 18 p.i. This clinical effect was associated with dose-dependent down-regulated production of IFN-gamma and the chemokines macrophage inflammatory protein-1 alpha (MIP-1 alpha, MIP-2 and monocyte chemotactic protein-1(MCP-1) as well as up-regulated IL-4 production in sciatic nerve sections from Rolipram-treated EAN rats at maximum of clinical EAN, i.e. on day 14 p.i.. These findings suggest that Rolipram may be useful in certain T cell-dependent autoimmune diseases and inflammatory neuropathies. These observations call for further studies on the potential role of Rolipram in the treatment of autoimmune diseases.
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