Suppression of chronic experimental autoimmune neuritis by nasally administered recombinant rat interleukin-6.
Experimental autoimmune neuritis (EAN) is a CD4+ T-cell-mediated demyelinating disease of the peripheral nervous system (PNS) and serves as experimental model for human immune-demyelinating neurophathies, especially the Guillain-Barré syndrome. In this study, we examined the effect of recombinant rat interleukin-6 (rrIL-6) on chronic EAN in Lewis rats induced by immunization with P2 peptide 57-81 and Freund's complete adjuvant (FCA). Nasal administration of rat rIL-6 (1 microg/rat/day) beginning in the initial phase of EAN as a therapeutic agent, decreased the severity and the duration of clinical EAN. Low-grade inflammation and suppression of regional demyelination within the sciatic nerves were seen in rrIL-6-treated rats. Hyporesponsiveness of lymph node T cells, down-regulation of serum tumour necrosis factor-alpha (TNF-alpha) and increased levels of P2-specific immunoglobulin G1 (IgG1) antibodies document that nasal administration of rrIL-6 was effective systemically. However, because of the non-specific nature of the treatment and multiple effects of IL-6, more experience and great caution are needed, before nasal administration of IL-6 can be considered as a treatment of human autoimmune demyelinating neurophathies.
Deretzi
G
G
Division of Neurology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
Pelidou
S
S
Zou
L
L
Quiding
C
C
Mix
E
E
Levi
M
M
Wahren
B
B
Zhu
J
J
D000281:Administration, Intranasal; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D002908:Chronic Disease; D004306:Dose-Response Relationship, Immunologic; D007074:Immunoglobulin G / Q000096:biosynthesis; D007165:Immunosuppression Therapy; D015850:Interleukin-6 / Q000627:therapeutic use*; D008297:Male; D009444:Neuritis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000627:therapeutic use; D012584:Sciatic Nerve / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007074:Immunoglobulin G; D015850:Interleukin-6; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha