期刊
INTERNATIONAL IMMUNOLOGY
卷 13, 期 6, 页码 825-833出版社
OXFORD UNIV PRESS
DOI: 10.1093/intimm/13.6.825
关键词
autoimmunity; IL-10; mucosa; tolerance
类别
资金
- NIAID NIH HHS [AI43458] Funding Source: Medline
- NINDS NIH HHS [NS38037] Funding Source: Medline
IL-10 is an immunoregulatory cytokine that can modulate immune processes, inhibiting the expression of inflammatory T(h)1 type responses as well as affecting antigen-presenting cell function. In addition, IL-10 has been shown to be active at mucosal surfaces, in the present study, we examined the role of IL-10 on orally and nasally induced tolerance. Treatment of(PL/J x SJL)F-1 mice with low-dose oral myelin basic protein (MBP) (0.5 mg) and simultaneous oral IL-10 given 3 times reduced the severity and incidence of experimental autoimmune encephalomyelitis (EAE), whereas administration of oral IL-10 alone or MBP alone given in these doses had no effect, Lymphocytes From mice treated orally with Map and IL-10 proliferated less, and produced decreased amounts of IFN-gamma and IL-2 and increased amounts of IL-10 and transforming growth factor-beta upon in vitro stimulation with MBP. Nasal administration of antigen and IL-10 reduced proliferative responses and IFN-gamma production, increased IL-10 production, and enhanced protection from EAE. In addition, oral IL-10 combined with oral myelin oligodendrocyte glycoprotein (MOG) 35-55 reduced relapses in MOG-induced EAE in the NOD mouse, as well as enhanced the protective effect of oral insulin in the NOD model of diabetes, These results demonstrate that IL-10 is biologically active at mucosal surfaces and can act synergistically to enhance the tolerogenic effects of mucosally administered antigen.
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