Treatment with P2 protein peptide 57-81 by nasal route is effective in Lewis rat experimental autoimmune neuritis.
Experimental autoimmune neuritis (EAN) is a CD4+ T cell-mediated autoimmune disorder of the peripheral nervous system (PNS) that can be actively induced in susceptible animal species and strains by active immunization with PNS myelin + Freund's complete adjuvant (FCA). EAN represents an animal model for studying the immunopathogenesis and treatment of Guillain-Barré syndrome (GBS), which is a major inflammatory demyelinating disease of the PNS in humans. Here, we report that treatment by nasal administration of the neuritogenic peptide 57-81 of the PNS myelin component, P2 protein, dose-dependently suppressed EAN severity and shortened clinical EAN. Clinical EAN relapse induced by rechallenge with BPM + FCA was also prevented in EAN rats receiving high dose P2 peptide. P2 peptide induced suppression of EAN was associated with PNS antigen specific T cell hyporesponsiveness reflected by lymphocyte proliferation, numbers of PNS antigen-reactive IFN-gamma secreting and IFN-gamma mRNA expressing lymph node cells, but elevated levels of PNS antigen reactive TGF-beta mRNA secreting cells. Reduced CD4+ T cell and macrophage infiltrations within the PNS were also observed. Based on these observations, nasal autoantigen administration should be further evaluated, considering its possible future use in GBS.
Zou
L P
LP
Division of Neurology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
Zhu
J
J
Deng
G M
GM
Levi
M
M
Wahren
B
B
Diab
A
A
Hillert
J
J
Link
H
H
D000281:Administration, Intranasal; D000595:Amino Acid Sequence; D000818:Animals; D016207:Cytokines / Q000235:genetics; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D018996:Myelin P2 Protein / Q000008:administration & dosage / Q000627:therapeutic use*; D009444:Neuritis, Autoimmune, Experimental / Q000188:drug therapy* / Q000473:pathology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew
D016207:Cytokines; D018996:Myelin P2 Protein; D010446:Peptide Fragments; D012333:RNA, Messenger