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LV Rizzo, HM Serra, LD Vieira de Moraes, AP Martin, A Gonçalves Commodaro; The Use of a VLA-4 Antagonist in Immune Modulation of Experimental Autoimmune Uveitis . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1540.
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Purpose: To study the immunodulatory effects of a VLA-4 antagonist (a/VLA-4)peptide in experimental autoimmune uveitis (EAU). Methods: B10.A mice were immunized on day 0 with IRBP to induce EAU and divided into four experimental groups (n=10). Animals from group I and II were injected intravenously with 10 mg of a/VLA-4 or an irrelevant peptide on days 2, 4 and 6 (afferent phase) and animals from group III and IV injected with the same peptides on days 14, 16 and 18 (efferent phase). Disease scores and the specific immune response to IRBP [DTH, serum antibodies, lymphoproliferative response and cytokines production (IL-2,4, 5, 13, 12, 18, 10, IFNg, TGFb) were studied on day 21. Results: A significant inhibition (P<0.05) of the EAU incidence, disease scores and DTH was observed when a/VLA-4 was administered during the efferent phase of the immune response. Mice so treated showed an increase of IL-18 and a decrease of IL-10 and anti-IRBP IgG1 antibodies. Interestingly, the lymphoproliferative response, IFNg, IL-2 and IL-12 levels were similar to those of the control animals. On the other hand, the use of the a/VLA-4 during the induction of EAU did not affect disease scores, DTH, lymphoproliferative response and levels of INFg, IL-2 and IL-12. Interestingly, it resulted in an increase in IL-18 and anti-IRBP IgG2a antibodies Conclusion: Our data suggest that a/VLA-4 administered during the efferent phase of EAU decrease the incidence and clinical manifestations of the disease, probably by blocking extravasation of effector cells. However, a/VLA-4 was ineffective in changing the course of disease when administered in the afferent phase of the immune response.
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