Mucosal administration of IL-10 enhances oral tolerance in autoimmune encephalomyelitis and diabetes

IL-10 is an immunoregulatory cytokine that can modulate immune processes, i nhibiting the expression of inflammatory T(h)1 type responses as well as af fecting antigen-presenting cell function. In addition, IL-10 has been shown to be active at mucosal surfaces, in the present study, we examined the ro le of IL-10 on orally and nasally induced tolerance. Treatment of(PL/J x SJ L)F-1 mice with low-dose oral myelin basic protein (MBP) (0.5 mg) and simul taneous oral IL-10 given 3 times reduced the severity and incidence of expe rimental autoimmune encephalomyelitis (EAE), whereas administration of oral IL-10 alone or MBP alone given in these doses had no effect, Lymphocytes F rom 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 a dministration 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 glyc oprotein (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 ef fects of mucosally administered antigen.