Mucosal administration of IL-10 enhances oral tolerance in autoimmune encephalomyelitis and diabetes.
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 MBP 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.
Slavin
A J
AJ
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Maron
R
R
Weiner
H L
HL
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000281:Administration, Intranasal; D000284:Administration, Oral; D000818:Animals; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000517:prevention & control*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D007108:Immune Tolerance; D018928:Immunity, Mucosal; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007279:Injections, Subcutaneous; D016753:Interleukin-10 / Q000008:administration & dosage*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D008815:Mice, Inbred Strains; D009061:Mouth Mucosa / Q000276:immunology*; D004676:Myelin Basic Protein / Q000008:administration & dosage / Q000494:pharmacology; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000008:administration & dosage; D063308:Myelin-Oligodendrocyte Glycoprotein; D009297:Nasal Mucosa / Q000276:immunology*; D012008:Recurrence
D000276:Adjuvants, Immunologic; D016207:Cytokines; D007166:Immunosuppressive Agents; C571327:Mog protein, mouse; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D016753:Interleukin-10