[Inhibiton of experimental autoimmune encephalomyelitis in Lewis rats by nasal administration of encephalitogenic MBP peptides: synergistic effects of MBP 68-86 and 87-99].
OBJECTIVE
To explore the synergistic effect of MBP 68-86 and 87-99, on the inhibition of experimental autoimmune encephalomyelitis (EAE) in Lewis rat by nasal administration.


METHODS
Three different MBP peptides(MBP 68-86, 87-99, and the non-encephalitogenic peptide 110-128) were synthesized and administrated nasally to Lewis rat on day-11, -10, -9, -8 and -7 prior to immunization with the guinea pig MBP (gp-MBP)+CFA, which was used to induce EAE. The protective effect on Lewis rat from EAE by the MBP peptides was evaluated.


RESULTS
Protection was achieved with the encephalitogenic peptides MBP 68-86 and 87-99, MBP 68-86 being more potent, but not with MBP 110-128. Neither MBP 68-86 nor 87-99 used alone conferred complete protection to gp-MBP-induced EAE. In contrast, nasal administration of a mixture of MBP 68-86 and 87-99 completely blocked gp-MBP-induced EAE even at lower dosage than being used alone. Rats tolerized with MBP 68-86+87-99 nasally showed decreased T cell responses to MBP, reflected by lymphocyte proliferation and IFN-gamma ELISPOT assays. Rats tolerized with MBP 68-86+87-99 also had abrogated MBP-reactive IFN-gamma and TNF-alpha mRNA expression in lymph node cells compared to rats receiving MBP 110-128 nasally, while similar low levels of MBP-reactive TGF-beta and IL-4 mRNA expressing cells were observed in the two groups.


CONCLUSIONS
Nasal administration of encephalitogenic MBP peptides can induce antigen-specific T cell tolerance and confer incomplete protection to gp-MBP-induced EAE, and MBP 68-86 and 87-99 have synergistic effects. Non-regulatory mechanisms are proposed to be responsible for tolerance development after nasal peptide administration.
Sun
Bo
B
Department of Neurobiology, Harbin Medical University, Harbin 150086, China. sunbo720@yahoo.com.cn
Yang
Shuo
S
Peng
Hai-sheng
HS
Qiao
Hui
H
Cao
Jing-yan
JY
Jin
Lian-hong
LH
Li
Hu-lun
HL
D000281:Administration, Intranasal; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy*; D017403:In Situ Hybridization; D007371:Interferon-gamma / Q000235:genetics; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects; D004676:Myelin Basic Protein / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D004676:Myelin Basic Protein; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma