Nasal administration of recombinant rat IL-4 ameliorates ongoing experimental autoimmune neuritis and inhibits demyelination

J Autoimmun. 1999 Mar;12(2):81-9. doi: 10.1006/jaut.1998.0259.

Abstract

Experimental autoimmune neuritis (EAN) is a CD4(+)T cell-mediated demyelinating disease of the peripheral nervous system (PNS) and serves as an experimental model for human immune-demyelinating neuropathies. In this study, we examined the effect of recombinant rat interleukin-4 (rrIL-4) on chronic EAN in Lewis rats induced by immunization with P0 peptide 180-199 and complete Freund's adjuvant (CFA). We estimated that nasal administration of rrIL-4, in dose ranges of 0.1-1 microg/rat/day in the initial phase of EAN, decreased the severity and the duration of clinical EAN. Hyporesponsiveness of T cells, downregulation of Th1 cell responses (INF-gamma), but increased levels of specific IgG1 isotypes document that nasal administration of rrIL-4 was systemically immune effective. Low grade inflammation and complete lack of regional demyelination within the sciatic nerves were seen in rrIL-4 treated rats. Based on these observations we suggest that nasal administration of IL-4 could be further evaluated, considering its possible use in human immune-demyelinating neuropathies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Animals
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / pathology
  • Autoimmune Diseases / therapy*
  • Demyelinating Diseases / immunology
  • Demyelinating Diseases / pathology
  • Demyelinating Diseases / therapy*
  • Disease Models, Animal
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / classification
  • Interferon-gamma / metabolism
  • Interleukin-4 / administration & dosage*
  • Lymphocyte Activation
  • Male
  • Neuritis / immunology
  • Neuritis / pathology
  • Neuritis / therapy*
  • Rats
  • Rats, Inbred Lew
  • Recombinant Proteins / administration & dosage

Substances

  • Immunoglobulin G
  • Recombinant Proteins
  • Interleukin-4
  • Interferon-gamma