Nasal administration of recombinant rat IL-4 ameliorates ongoing experimental autoimmune neuritis and inhibits demyelination.
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.
Division of Neurology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
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G
Deretzi
L P
LP
Zou
S H
SH
Pelidou
I
I
Nennesmo
M
M
Levi
B
B
Wahren
E
E
Mix
J
J
Zhu
D000281:Administration, Intranasal; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D003711:Demyelinating Diseases / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000008:administration & dosage*; D008213:Lymphocyte Activation; D008297:Male; D009443:Neuritis / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000008:administration & dosage
D007074:Immunoglobulin G; D011994:Recombinant Proteins; D015847:Interleukin-4; D007371:Interferon-gamma