Suppression of acute and protracted-relapsing experimental allergic encephalomyelitis by nasal administration of low-dose IL-10 in rats.
In this study we report for the first time that nasal administration of the Th2 cell-related cytokine interleukin-10 (IL-10), at concentrations of 1.5 microg/rat and 15 microg/rat, suppressed clinical signs of acute experimental allergic encephalomyelitis (EAE) in Lewis rats and prevented the development and relapse of protracted-relapsing EAE (PR-EAE) in DA rats. In contrast, subcutaneous injection of IL-10 (15 microg/rat) did not inhibit acute EAE. The IL-10-mediated suppression of EAE was associated with decreased myelin antigen-specific T-cell proliferative responses and IFN-gamma secretion in both acute and PR-EAE. In sections of spinal cords derived from rats nasally pretreated with IL-10, there were no infiltrating CD4+ T cells or macrophages, which are considered as major encephalitogenic or inflammatory cells. Most interestingly, nasally administered IL-10 also inhibited MHC class II expression in microglia, indicating that IL-10 administration by the nasal route prevents the activation of microglia. Administration of cytokines via the nasal route offers an exciting alternative in the prevention and treatment of autoimmune diseases.
Xiao
B G
BG
Division of Neurology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
Bai
X F
XF
Zhang
G X
GX
Link
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H
D000208:Acute Disease; D000281:Administration, Intranasal; D000818:Animals; D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D006168:Guinea Pigs; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007150:Immunohistochemistry; D007167:Immunotherapy / Q000379:methods; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000008:administration & dosage*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D017628:Microglia / Q000276:immunology / Q000378:metabolism; D004676:Myelin Basic Protein / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D012008:Recurrence; D013116:Spinal Cord / Q000166:cytology / Q000276:immunology
D015415:Biomarkers; D000949:Histocompatibility Antigens Class II; D004676:Myelin Basic Protein; D016753:Interleukin-10; D007371:Interferon-gamma