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Hisashi Mashimo, Nobuyuki Ohguro, Shintaro Nomura, Noriyasu Hashida, Kei Nakai, Yasuo Tano; Neutrophil Chemotaxis and Local Expression of Interleukin-10 in the Tolerance of Endotoxin-Induced Uveitis. Invest. Ophthalmol. Vis. Sci. 2008;49(12):5450-5457. doi: 10.1167/iovs.08-1878.
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© ARVO (1962-2015); The Authors (2016-present)
purpose. To study the mechanism of lipopolysaccharide (LPS) tolerance in a rat model of footpad injection endotoxin-induced uveitis (EIU).
methods. EIU was produced by footpad injection of 1 mg/kg LPS in male Sprague-Dawley rats. Four experiments were undertaken in this study. First, on days 3, 7, 14, 28, 56, and 84 after LPS injection, the iris-ciliary body (ICB) was isolated. LPS tolerance-associated gene expression in the ICB was determined by quantitative polymerase chain reaction. Second, the distribution of IL-10–producing cells in frozen sections of ocular tissues was analyzed by fluorescence and confocal microscopy. Third, peripheral blood neutrophil chemotaxis was determined using a fluorescent in vitro migration assay. Fourth, for in vivo neutrophil chemotaxis assay, neutrophils isolated from EIU-tolerant or control rats were transfused into green fluorescence protein (GFP) rats injected with LPS 18 hours earlier. Six hours after transfusion, the percentage of GFP-negative neutrophils in the aqueous humor was determined by flow cytometry.
results. IL-10 gene expression in ICB was significantly upregulated for at least 1 month. Immunohistochemical examination indicated that dendritic cells in the ICB produced IL-10. Peripheral blood neutrophil chemotaxis in EIU-tolerant rats was inhibited significantly in vitro and in vivo. IL-10 enhanced the reduction of neutrophil chemotaxis in EIU-tolerant rats in vitro.
conclusions. The results suggest that continuous high expression of IL-10 in the eye and the reduction of peripheral blood neutrophil chemotaxis play significant roles in the mechanism of LPS tolerance in a rat model of footpad injection EIU.
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