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W. Zhang, M. Rojas, N.-T. Tsai, D. T. Nguyen, R. W. Caldwell, R. B. Caldwell; Deficiency of Interleukin-6 Prevents Acute Retinal Inflammation. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3572.
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Inflammation is believed to play a critical role in the pathogenesis of a variety of retinal diseases such as uveitis, diabetic retinopathy and ischemic retinopathy. Interleukin-6 (IL-6) has been implicated in retinopathy given that its expression is increased in vitreous from patients with uveitis or diabetic retinopathy. However, its specific role in these diseases has not been addressed. Here we determined the role of IL-6 in acute retinal inflammation in endotoxin-induced uveitis (EIU).
C57BL/6 wild type (WT) or IL-6 knockout (IL-6ko) mice were injected with lipopolysaccharide (LPS 1 mg/kg, i.p.) to induce EIU. Expression of cytokines in retina and cultured cells was determined by real-time quantitative PCR and ELISA. Leukocytes adherent to the wall of the retinal vessels (leukostasis) was evaluated by perfusion-labeling of the vessels and leukocytes with fluorescent concanavalin A.
Expression of IL-6 in the retina was robustly increased in the LPS-treated mice, with a peak mRNA increase at 6h. Consistent with mRNA level, IL-6 protein was also significantly increased as measured by ELISA. Incubation of primary Muller cells with LPS resulted in strong IL-6 expression as well. Associated with the expression of IL-6, inflammatory genes, such as CCL2, ICAM-1, iNOS, and TNF-alpha were prominently increased in WT mice 6h after LPS treatment. However, LPS-induced expression of CCL2, ICAM-1 and iNOS was significantly reduced in IL-6ko mice by 85%, 57% and 91%, respectively. In contrast, expression of TNF-alpha was not affected, suggesting an independent regulatory mechanism. Leukostasis is a common feature of retinal inflammation and is an important step in leukocyte infiltration. Associated with the reduction of inflammatory genes, LPS-induced leukostasis was significantly attenuated in IL-6 deficient mice as compared with WT mice.
IL-6 expression is increased in acute retinal inflammation and is necessary for the inflammatory response. Blockade of IL-6 may provide a therapeutic approach for the treatment of retinal inflammation in retinopathy.
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