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Exp Neurol ; 163(1): 165-72, 2000 May.
Article in English | MEDLINE | ID: mdl-10785455

ABSTRACT

Experimental autoimmune neuritis (EAN) is a CD4(+) T-cell-mediated demyelinating disease of the peripheral nervous system (PNS). We examined the effect of recombinant mouse interleukin 17 (rmIL-17) on chronic EAN induced in Lewis rats by inoculation of P2 57-81 peptide in Freund's complete adjuvant. Animals were treated nasally for 6 days with either 0.1 or 0.9 microg/rat/day rmIL-17 from the onset of neurological signs, i.e., days 9 to 14 postimmunization (p.i.). Prolonged follow-up demonstrated a chronic course in control and rmIL-17-treated rats. Treated rats had more severe disease initially (days 18-36 p.i.) with a stronger enhancing effect observed with the higher rmIL-17 dose. At day 19 rmIL-17-treated rats showed increased infiltration of inflammatory cells into the sciatic nerve, more severe demyelination, augmented proliferation of regional lymph node cells, and increased serum levels of tumor necrosis factor-alpha. After the initial phase of disease enhancement the IL-17-treated EAN rats improved gradually and ultimately recovered completely, whereas the control EAN rats remained affected until the end of the observation (day 120 p.i.). The lower dose of rmIL-17 induced an earlier recovery from clinical deficits than the higher one. The results indicate that IL-17 plays an immunoregulatory role in chronic EAN which could have implications for immunomodulatory treatments of chronic autoimmune disease of the PNS.


Subject(s)
Interleukin-17/immunology , Neuritis, Autoimmune, Experimental/immunology , Acute Disease , Administration, Intranasal , Animals , Cells, Cultured , Chronic Disease , Disease Progression , Dose-Response Relationship, Drug , Immunohistochemistry , Interleukin-17/administration & dosage , Leukocytes, Mononuclear/cytology , Leukocytes, Mononuclear/drug effects , Lymphocyte Activation/drug effects , Lymphocyte Activation/immunology , Male , Mice , Myelin P2 Protein/immunology , Neuritis, Autoimmune, Experimental/pathology , Peptide Fragments/immunology , Rats , Rats, Inbred Lew , Recombinant Proteins/administration & dosage , Recombinant Proteins/immunology , Recombinant Proteins/therapeutic use , Sciatic Nerve/drug effects , Sciatic Nerve/pathology , Tumor Necrosis Factor-alpha/metabolism
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