Combined nasal administration of encephalitogenic myelin basic protein peptide 68-86 and IL-10 suppressed incipient experimental allergic encephalomyelitis in Lewis rats.
Mucosal administration of low doses of myelin basic protein (MBP) peptide 68-86 (MBP 68-86) or anti-inflammatory cytokine IL-10 effectively prevented experimental allergic encephalomyelitis (EAE), but failed to suppress the disease if given after 7 days postimmunization (p.i.), i.e., after T cell priming had occurred. We anticipated that combined administration of autoantigen and IL-10 can treat incipient EAE. Lewis rats with EAE actively induced with MBP 68-86 and complete Freund's adjuvant received 120 microg MBP 68-86 + 200 ng IL-10 per rat per day from day 7 p.i. and for 5 consecutive days. These rats showed later onset, lower clinical scores, less body weight loss, and shorter duration of EAE than rats receiving MBP 68-86 or IL-10 only or PBS. EAE amelioration was associated with decreased infiltration of ED1(+) macrophages and CD4(+) T cells within the central nervous system and with decreased proliferative responses of lymph node cells, indicating that combined administration of MBP 68-86 and IL-10 induced immune hyporesponsiveness. IFN-gamma secretion as well as IFN-gamma, TNF-alpha, IL-4, and IL-10 mRNA expression by lymph node MNC was down-regulated in the treated rats. Immune hyporesponsiveness, rather than immune deviation or regulatory mechanisms, seems to be responsible for the protection of EAE after autoantigen + IL-10 administration by the nasal route.
Xu
L Y
LY
Experimental Neurobiology Unit and Neuroimmunology Unit, Karolinska Institute, Stockholm, Sweden.
Yang
J S
JS
Huang
Y M
YM
Levi
M
M
Link
H
H
Xiao
B G
BG
D000281:Administration, Intranasal; D000284:Administration, Oral; D000818:Animals; D000941:Antigens / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics; D004359:Drug Therapy, Combination; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control; D007108:Immune Tolerance / Q000187:drug effects; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000008:administration & dosage* / Q000627:therapeutic use*; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation / Q000187:drug effects; D009000:Monocytes / Q000737:chemistry; D004676:Myelin Basic Protein / Q000008:administration & dosage* / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D018417:Th1 Cells / Q000378:metabolism
D000941:Antigens; D016207:Cytokines; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D012333:RNA, Messenger; C110235:myelin basic protein 68-86; D016753:Interleukin-10; D007371:Interferon-gamma