Enhancement of acute phase and inhibition of chronic phase of experimental autoimmune neuritis in Lewis rats by intranasal administration of recombinant mouse interleukin 17: potential immunoregulatory role.
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.
Pelidou
S H
SH
Division of Geriatric Medicine, Huddinge University Hospital, Stockholm, S-141 86, Sweden.
Zou
L P
LP
Deretzi
G
G
Oniding
C
C
Mix
E
E
Zhu
J
J
D000208:Acute Disease; D000281:Administration, Intranasal; D000818:Animals; D002478:Cells, Cultured; D002908:Chronic Disease; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000008:administration & dosage / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D018996:Myelin P2 Protein / Q000276:immunology; D009444:Neuritis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D010446:Peptide Fragments / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D012584:Sciatic Nerve / Q000187:drug effects / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D020381:Interleukin-17; D018996:Myelin P2 Protein; D010446:Peptide Fragments; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha