P95. Immunmodulatory effects of intrathecal administration of triamcinolone in experimental autoimmune neuritis model in lewis rats

Abstract

Objective We studied the immunmodulatory effects of triamcinolone applied intrathecally in the animal model of experimental autoimmune neuritis (EAN) in Lewis rats. Background Therapeutic efficacy of intravenous corticosteroids in chronic autoimmune neuritis has been shown in several randomized, placebo-controlled studies, although the exact mechanisms of action remain unclear. Intrathecal drug administration is an alternate route of delivery in order to bypass the blood-nerve barrier and achieve a direct effect on the nerve roots. Methods Active EAN was induced by immunization with the P2 aa 53–78 myelin peptide in Lewis rats followed by intrathecal application of 0.6 mg/kg or 1.2 mg/kg traimcinolone once daily on day 11 p.i (post-immunisation). The clinical severity score was assessed daily until day 23 p.i.. Nerve conduction studies and histological analyses of the sciatic nerves for demyelination and inflammatory infiltrates as well as flow cytometric analyses of the peripheral lymph nodes and spleen were performed at the disease maximum (day 18 p.i.). Results Therapeutic treatment with 0.6 and 1.2 mg/kg Triamcinolone applied intrathecally on day 11 p.i. significantly ameliorated clinical signs of neuritis by reducing proximal as well as distal demyelination in the nerve conduction studies. Further, histological analyses revealed a significantly lower degree of T cells and macrophages infiltrates accompanied with a decrease of proinflammatory cytokines (IFN-g and TNF-a) and an increase of anti-inflammatory cytokines (IL-10, IL-4) in the sciatic nerves at the disease maximum. Furthermore, Schwann cells death markers (caspase-3) showed a reduced Schwann cells apoptosis on triamcinolone treatment. Conclusions Intrathecal administration of triamcinolone in the rat model of autoimmune neuritis is a safe and effective immunomodulatory option with a anti-degenerative potential. Further studies are required in order to investigate the safety and efficacy of intrathecal triamcinolone application in patients with autoimmune neuritis.