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4-Integrin Inhibits the Development of Experimental Autoimmune Uveitis
1From the Department of Immunology, Biomedical Sciences Institute, University of São Paulo, São Paulo, Brazil; 3Departamento Bioquímica Clínica, Inmunología, Facultad Cs, Químicas, UNC, Argentina; 4Clínica Reina Fabiola, Córdoba, Argentina; 5División Inmunogenética, Hospital de Clínicas "José de San Martín," Universidad de Buenos Aires, Buenos Aires, Argentina; 6LIM-60, University of São Paulo Medical School and Fundação Zerbini, São Paulo, Brazil; and 7Instituto de Investigação em Imunologia (iii), Ministério da Ciência e Tecnologia, Salvador, Brazil.
PURPOSE. Recruitment of lymphocytes into the retina and to the vitreous during the development of experimental autoimmune uveitis (EAU) is governed by factors such as the state of activation of inflammatory cells and the repertoire of adhesion molecules expressed by the local vascular endothelia. 
4 Integrins and their receptors play an important role during homing of cells to the inflammatory site. In the present study, the effect of 4-integrin inhibitor on the development of EAU was investigated.
METHODS. EAU was induced either by immunizing B10.RIII mice with the 161-180 peptide or by adoptive transfer of interphotoreceptor retinoid-binding protein (IRBP)–specific uveitogenic T cells. Animals were treated with an active peptide inhibitor (4-api) or a peptide control at different time points after induction of disease. EAU was evaluated by histology 21 to 49 days after immunization. Antigen-specific cell proliferation was evaluated by thymidine incorporation. Cytokine synthesis in culture supernatants and anti-IRBP-specific serum IgG1 and IgG2a were evaluated by ELISA. Delayed-type hypersensitivity was evaluated by ear challenge 2 days before the termination of the experiment.
RESULTS. Treatment with 4-api had a significant ameliorating effect on EAU. The anti-IRBP antibody response and cellular proliferation were not affected by the treatment, whereas delayed-type hypersensitivity was significantly diminished. Cytokine synthesis was not changed by treatment, except for a decrease in IL-10 levels.
CONCLUSIONS. The results show that small-molecule inhibitors of 4-integrins can act therapeutically in EAU, possibly by interfering with cell adhesion events involved in the development of the disease.
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