Characterization Of a New Animal Model Of Chronic Inflammatory Demyelinating Polyneuropathy (P1.061)

OBJECTIVE Characterize a new animal model of chronic inflammatory demyelinating polyneuropathy (CIDP). BACKGROUND Guillain-Barre syndrome (GBS) and CIDP are autoimmune-mediated inflammatory diseases of the peripheral nervous system. Most of the knowledge about GBS pathogenesis has been obtained through studies of the animal model of experimental autoimmune neuritis (EAN). At the moment, there is no useful animal model for CIDP. Previously we have shown that the thiopalmitoylated peptide S-palmP0(180-199) is able to induce a chronic EAN in Lewis rats. DESIGN/METHODS Lewis rats were immunized with peptide P0(180-199) (EAN rats) or S-palmP0(180-199) (chronic rats). Animals were assessed daily for clinical signs. We evaluated at 18, 40 and 60 days post injection (dpi) the electrophysiological profile, cytokine concentrations and anti-P0(180-199) antibody levels in serum (ELISA). An immunohistological analysis of sciatic nerves and spinal nerve roots at 74 dpi evaluated myelin, axons, cell infiltrations and interleukine-17. RESULTS Rats injected with P0(180-199) developed a classical monophasic disease while rats injected with S-palmP0(180-199) developed a chronic form. Electrophysiological studies suggest a severe and persistent demyelination, an axonal degeneration and the presence of conduction blocks in chronic rats compared to EAN rats. Serum production of IL-17 was significantly higher in chronic rats. At 60 dpi anti-P0(180-199) levels were higher in chronic rats compared to EAN rats. In chronic rats immunohistological examination of sciatic nerve revealed a marked demyelination followed by remyelination with smaller diameter fibers, and axonal depletion. T lymphocyte and mainly macrophage infiltrations were higher in chronic compared to EAN rats. Accumulation of IL-17 positive cells was important in spinal nerve roots of chronic animals. CONCLUSIONS We describe a new model of chronic EAN that can be easily and reliably induced by active immunization with S-palmP0(180-199) peptide with an incidence of 100%. Electrophysiological, immunological and immonohistological features are similar to the human CIDP. This model will be useful for understanding the pathophysiological mechanisms of CIDP and exploring new therapeutic strategies. Disclosure: Dr. Kremer has nothing to disclose. Dr. Brun has nothing to disclose. Dr. Beaino has nothing to disclose. Dr. Taleb has nothing to disclose. Dr. Lam has nothing to disclose. Dr. Collongues has nothing to disclose. Dr. Trifilieff has nothing to disclose. Dr. De Seze has nothing to disclose.