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D. Shen, H. Ramkumar, X. Cao, J. Tuo, C.-C. Chan; Cytokine Expression in Inflammatory Cells of Non-Infectious Uveitis. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5860.
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T-cell-dependent autoimmunity plays a critical role in the pathogenesis of non-infectious uveitis. A novel T-helper (Th) cell subset, Th17, produces the pro-inflammatory cytokines IL17 and IL22 and is an important effector cell in inflammation. IL-6 is critical for the priming of Th17 responses. IL-23 induces Th17 differentiation and promotes Th17 survival. RORC is essential for the development of Th17 cells. We studied the expression of T-cell cytokines and Th17-related cytokines in the vitreous of uveitic patients.
Twelve non-infectious uveitis cases (8 female and 4 male, ages 47 - 87 years old) underwent diagnostic vitrectomy. The medical records were reviewed. The vitreous cytospin slides from each case were examined and inflammatory cells were microdissected for RNA isolation and cDNA synthesis. Real-time PCR was performed to check IL4, IL6, IFNγ, IL17, IL23, and RORC expression. Human universal RNA was used as reference. Vitreous IL-6 levels were measured by ELISA.
Eleven out of the 12 cases had active posterior inflammation and decreased visual acuity. On each slide, mostly lymphocytes and some macrophages were observed. Seven cases with >2+ vitritis and posterior haze were categorized as high inflammation (H), and 5 cases with <2+ vitritis were categorized low inflammation (L). Compared to human universal RNA as 1, inflammatory cell mRNA expression of IFNγ in H and L was 155.49±185.51 and 45.83±63.23 folds; IL6 was 7.49±7.05 and 1.50±1.11 folds; and IL4 was 0.43±0.66 and 0.68±0.59 folds. The expression of IL23, RORC, and IL17 in H and L were 4.20±5.75 and 2.17±2.42, 6.94±6.72 and 4.58±4.41, and 6.87±11.37 and 3.24±4.05 folds, respectively. Vitreous IL-6 levels were elevated to 68.70±85.04 pg/ml in H and 26.08±19.92 pg/ml in L (normal range: 0-0.2 pg/ml), which correlated with the severity of ocular inflammation.
High IFNγ expression in inflammatory cells demonstrates a Th1 cell-mediated immune response in most posterior uveitic cases. Few IL4 transcripts suggest minimal Th2 cells in the vitreous of non-infectious uveitis. The expression profile of IL23, RORC, and IL17 suggests that IL-17 and Th17 responses have a role in human uveitis. Our data support the notion that human uveitis is driven by both Th1 and Th17 cells. Understanding and modulating Th17 cells and Th17 may provide new therapeutic strategies for uveitis.
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