IL-10 has a protective role in experimental autoimmune uveoretinitis.
The role of IL-10 in the regulation of ocular autoimmune disease was studied in experimental autoimmune uveoretinitis (EAU) elicited in mice by immunization with the retinal antigen interphotoreceptor retinoid binding protein. IL-10-deficient mice were susceptible to EAU, indicating that pathogenesis can occur without presence of IL-10. Treatment of normal mice with IL-10 for 5 days after uveitogenic immunization ameliorated subsequent EAU scores, and down-regulated antigen-specific production of tumor necrosis factor-alpha and IFN-gamma. A concomitant treatment with IL-4 further reduced disease, and resulted in emergence of antigen-specific IL-4 and IL-10 production, as well as in enhancement of the IgG1 antibody isotype. IL-4 by itself was not protective. Only IL-10, but not IL-4, was able to inhibit the function of differentiated uveitogenic T cells in culture. Expression of mRNA for Th1 and Th2 cytokines in the eye during the course of EAU showed that while a Th1 pattern predominated early, IL-10 mRNA expression coincided with down-regulation of the Th1 response and resolution of EAU. Systemic neutralization of IL-10 during the expression phase of EAU resulted in elevated disease scores. Our results suggest that endogenous IL-10 limits expression of EAU and may play a role in the natural resolution of disease. The data further suggest that exogenous IL-10 may be useful in therapeutic control of autoimmune uveitis. While IL-10 by itself is sufficient to suppress Th1 effector development and function, a concomitant administration of IL-4 is required to shift the autoimmune response towards a non-pathogenic Th2 pathway.
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892-5897, USA.
L V
LV
Rizzo
H
H
Xu
C C
CC
Chan
B
B
Wiggert
R R
RR
Caspi
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy*; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007114:Immunization; D016753:Interleukin-10 / Q000172:deficiency / Q000276:immunology / Q000627:therapeutic use*; D015847:Interleukin-4 / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000008:administration & dosage; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000627:therapeutic use; D012173:Retinitis / Q000276:immunology / Q000628:therapy*; D012177:Retinol-Binding Proteins / Q000008:administration & dosage; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D013997:Time Factors
D016207:Cytokines; D010446:Peptide Fragments; D012333:RNA, Messenger; D011994:Recombinant Proteins; D012177:Retinol-Binding Proteins; C084433:interphotoreceptor-retinoid binding protein (1158-1180); D016753:Interleukin-10; D015847:Interleukin-4