International Immunology, Vol. 13, No. 6, 825-833,
June 2001
© 2001 Japanese Society for Immunology
Mucosal administration of IL-10 enhances oral tolerance in autoimmune encephalomyelitis and diabetes
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
Correspondence to: H. L. Weiner
IL-10 is an immunoregulatory cytokine that can modulate immune processes, inhibiting the expression of inflammatory Th1 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)F1 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-
and IL-2 and increased amounts of IL-10 and transforming growth factor-ß upon in vitro stimulation with MBP. Nasal administration of antigen and IL-10 reduced proliferative responses and IFN- 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.
Keywords: autoimmunity, IL-10, mucosa, tolerance
1 Present address: Division of Immunology & Rheumatology, Stanford University, Stanford, CA 94305, USA
Transmitting author: L. Steinman
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. K. Bliss, S. P. Bliss, D. P. Beiting, A. Alcaraz, and J. A. Appleton IL-10 Regulates Movement of Intestinally Derived CD4+ T Cells to the Liver J. Immunol., June 15, 2007; 178(12): 7974 - 7983. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Gianfrani, M. K. Levings, C. Sartirana, G. Mazzarella, G. Barba, D. Zanzi, A. Camarca, G. Iaquinto, N. Giardullo, S. Auricchio, et al. Gliadin-Specific Type 1 Regulatory T Cells from the Intestinal Mucosa of Treated Celiac Patients Inhibit Pathogenic T Cells J. Immunol., September 15, 2006; 177(6): 4178 - 4186. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Song, Z. Guan, I. E. Gienapp, T. Shawler, J. Benson, and C. C. Whitacre The Thymus Plays a Role in Oral Tolerance in Experimental Autoimmune Encephalomyelitis J. Immunol., August 1, 2006; 177(3): 1500 - 1509. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Bellavite, R. Ortolani, and A. Conforti Immunology and Homeopathy. 3. Experimental Studies on Animal Models Evid. Based Complement. Altern. Med., June 1, 2006; 3(2): 171 - 186. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Miyamoto, C. I. Kingsley, X. Zhang, C. Jabs, L. Izikson, R. A. Sobel, H. L. Weiner, V. K. Kuchroo, and A. H. Sharpe The ICOS Molecule Plays a Crucial Role in the Development of Mucosal Tolerance J. Immunol., December 1, 2005; 175(11): 7341 - 7347. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Safadi, C. E. Alvarez, M. Ohta, J. Brimnes, T. Kraus, W. Mehal, J. Bromberg, L. Mayer, and S. L. Friedman Enhanced Oral Tolerance in Transgenic Mice with Hepatocyte Secretion of IL-10 J. Immunol., September 15, 2005; 175(6): 3577 - 3583. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Nath, S. Giri, R. Prasad, M. L. Salem, A. K. Singh, and I. Singh 5-Aminoimidazole-4-Carboxamide Ribonucleoside: A Novel Immunomodulator with Therapeutic Efficacy in Experimental Autoimmune Encephalomyelitis J. Immunol., July 1, 2005; 175(1): 566 - 574. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. W. DePaolo, R. Lathan, and W. J. Karpus CCR5 Regulates High Dose Oral Tolerance by Modulating CC Chemokine Ligand 2 Levels in the GALT J. Immunol., July 1, 2004; 173(1): 314 - 320. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Ma, Y. Huang, Z. Yin, R. Menassa, J. E. Brandle, and A. M. Jevnikar Induction of oral tolerance to prevent diabetes with transgenic plants requires glutamic acid decarboxylase (GAD) and IL-4 PNAS, April 13, 2004; 101(15): 5680 - 5685. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. R. Mathers and C. F. Cuff Role of Interleukin-4 (IL-4) and IL-10 in Serum Immunoglobulin G Antibody Responses following Mucosal or Systemic Reovirus Infection J. Virol., April 1, 2004; 78(7): 3352 - 3360. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. W. DePaolo, B. J. Rollins, W. Kuziel, and W. J. Karpus CC Chemokine Ligand 2 and Its Receptor Regulate Mucosal Production of IL-12 and TGF-{beta} in High Dose Oral Tolerance J. Immunol., October 1, 2003; 171(7): 3560 - 3567. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Sundstedt, E. J. O'Neill, K. S. Nicolson, and D. C. Wraith Role for IL-10 in Suppression Mediated by Peptide-Induced Regulatory T Cells In Vivo J. Immunol., February 1, 2003; 170(3): 1240 - 1248. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Yin, G. Bahtiyar, N. Zhang, L. Liu, P. Zhu, M. E. Robert, J. McNiff, M. P. Madaio, and J. Craft IL-10 Regulates Murine Lupus J. Immunol., August 15, 2002; 169(4): 2148 - 2155. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G.-X. Zhang, H. Xu, M. Kishi, D. Calida, and A. Rostami The Role of IL-12 in the Induction of Intravenous Tolerance in Experimental Autoimmune Encephalomyelitis J. Immunol., March 1, 2002; 168(5): 2501 - 2507. [Abstract] [Full Text] [PDF]
|
|