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S.Q. Al-Khatib, Z. Li, P. Silver, D. Shen, H.N. Sen, R. Ursea, S.K. Srivastava, R.R. Buggage, C. Chan, R.B. Nussenblatt; Intravitreal Injection of Anti-interleukin-2 Receptor in Experimental Autoimmune Uveoretinitis (EAU) . Invest. Ophthalmol. Vis. Sci. 2003;44(13):724.
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Purpose: To evaluate the effect of a locally administered interleukin-2 receptor (IL-2R) blocking antibody on ocular inflammation in the afferent phase of EAU. Methods: EAU in B10.RIII mice was induced with 10 µg of human IRBP peptide 161-180 in PBS, emulsified 1:1 v/v in CFA. At day 7, animals were divided into three groups: (1) intravitreal injection of 3 µl (1.6mg/ml) of murinized rat anti-IL-2R antibody, 3c7-IgG 2a, in the right eye and 3 µl of buffered saline solution (BSS) in the left eye; (2) intravitreal injection of 3 µl of 3c7-IgG 2a in the right eye only; (3) no treatment. Fundoscopic evaluation for longitudinal follow-up of EAU was performed and scored. At day 14, all mice were killed. The eyes were harvested for histological grading. Statistics were performed with Stat View 4.5. Results: Clinically EAU developed in all three groups, although the Group (3) mice (no treatment) had significantly milder disease as compared to Groups (1) and (2). These findings were matched with histology (Table) (right eyes in group 1 and 2 vs. 3, p = 0.045). In general, the eyes receiving anti-IL-2R antibodies exhibited slightly greater inflammation as compared to the eyes without injection or injected with BSS. Interestingly, there was a relative increase in infiltrating granulocytes, particularly PMNs and a decrease of lymphocytes in the eyes treated with anti-IL-2R antibodies. Conclusions: 3c7-IgG 2a given in the late afferent phase may exacerbate ocular inflammation in a murine EAU model. Data suggest the inhibition of IL-2R might disturb the cytokine and or chemokine cascade in inflammation. The blockage of IL-2R in the afferent phase of an inflammatory process may serve as feedback signal to initiate a reflux of other inflammatory cells rather than T-lymphocytes into the target organ. Further experiments and study are needed and will provide useful information in the timing of anti-IL-2R antibody therapy for human uveitis. Clinical and Histological Scores (mean ± SEM) View OriginalDownload SlideView OriginalDownload Slide
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