Curto Elizabeth, Messenger Kristen M, Salmon Jacklyn H, Gilger Brian C
Department of Clinical Sciences, North Carolina State University College of Veterinary Medicine, Raleigh, NC 27607, USA.
Department of Molecular Biomedical Sciences, North Carolina State University College of Veterinary Medicine, Raleigh, NC 27607, USA.
Vet Immunol Immunopathol. 2016 Dec;182:43-51. doi: 10.1016/j.vetimm.2016.09.008. Epub 2016 Sep 27.
To determine whether horses with clinically diagnosed Equine Recurrent Uveitis (ERU) and those with Leptospirosis infection have a specific cytokine profile in their aqueous humor (AH) and serum that differs from horses with uveitis secondary to other ocular inflammatory processes and from horses with normal eyes.
Twenty-five client-owned horses with uveitis that were presented to the North Carolina State University Ophthalmology Service, and four University-owned horses without history or clinical signs of ocular disease.
Samples of AH and serum were obtained from horses with ERU (n=13), acute or non-recurrent uveitis (UV; n=7), uveitis secondary to infectious keratitis (IK; n=5), and normal eyes (N; n=4). Cytokine levels in AH and serum were quantified using a multiplex bead immunoassay. Leptospiral antibody titers in serum and AH and PCR for Leptospiral DNA in AH were performed.
In the AH of horses with ERU, increased levels of IL-1a, IL-4, IL-6, IL-8, IL-12p70, FGF-2, G-CSF, and RANTES were measured compared to UV, IK and N eyes, but the differences were not significant. However, IL-10 was significantly higher in ERU eyes compared to IK and N (P=0.029; 0.013), and IP-10 in ERU eyes was significantly higher than in UV and N (P=0.004). Furthermore, MCP-1 was significantly higher in ERU than N (P=0.04). In the serum, increased levels of IL-1a, IL-4, IL-6, IL-8, IL-12p70, fractalkine, and G-CSF were measured in horses with ERU, but the levels were not significantly higher than those observed in UV, IK, or N horses. However, serum IP-10 levels in horses with ERU were significantly higher than in UV and N horses (P=0.005) and MCP-1 levels were significantly higher in ERU than N (P=0.03). Horses with marked ocular inflammation had significantly higher serum levels of G-CSF, IL-1a, fractalkine, IL-13, IL-4, IL-17a, IL-12p70, IFN-γ, and MCP-1. Elevated IL-10 in AH was significantly associated with disease chronicity, both overall and in ERU eyes (P=0.049), and in horses with positive ocular leptospiral titers or leptospiral PCR, significant elevations of IL-10 (P=0.0018; 0.0032) and IP-10 (P=0.0342; 0.043) were detected in the AH compared to leptospiral negative eyes.
The anti-inflammatory cytokine IL-10 and the pro-inflammatory cytokine IP-10 appear to play an important role in ERU. Further studies are needed to further clarify and characterize cytokine profiles of specific ocular inflammatory diseases, but multiplex bead immunoassay technology shows promise as a diagnostically valuable tool.
确定临床诊断为马复发性葡萄膜炎（ERU）的马匹以及感染钩端螺旋体的马匹，其房水（AH）和血清中的特定细胞因子谱是否与继发于其他眼部炎症过程的葡萄膜炎马匹以及正常眼睛的马匹不同。
二十五匹由客户拥有的患有葡萄膜炎的马，这些马被送到北卡罗来纳州立大学眼科服务中心，以及四匹学校拥有的无眼部疾病病史或临床症状的马。
从患有ERU的马（n = 13）、急性或非复发性葡萄膜炎（UV；n = 7）、感染性角膜炎继发的葡萄膜炎（IK；n = 5）以及正常眼睛（N；n = 4）的马身上获取AH和血清样本。使用多重珠免疫测定法定量AH和血清中的细胞因子水平。检测血清和AH中的钩端螺旋体抗体滴度以及AH中的钩端螺旋体DNA的PCR。
与UV、IK和N组眼睛相比，在患有ERU的马的AH中，IL-1α、IL-4、IL-6、IL-8、IL-12p70、FGF-2、G-CSF和RANTES水平升高，但差异不显著。然而，与IK和N组相比，ERU组眼睛中的IL-10显著更高（P = 0.029；0.013），ERU组眼睛中的IP-10显著高于UV和N组（P = 0.004）。此外，ERU组中的MCP-1显著高于N组（P = 0.04）。在血清中，患有ERU的马中IL-1α、IL-4、IL-6、IL-8、IL-12p70、fractalkine和G-CSF水平升高，但这些水平并不显著高于UV、IK或N组马中观察到的水平。然而，患有ERU的马的血清IP-10水平显著高于UV和N组马（P = 0.005），ERU组中的MCP-1水平显著高于N组（P = 0.03）。眼部炎症明显的马血清中G-CSF、IL-1α、fractalkine、IL-13、IL-4、IL-17α、IL-12p70、IFN-γ和MCP-1水平显著更高。AH中IL-10升高与疾病慢性化显著相关，总体上以及在ERU组眼睛中均如此（P = 0.049），并且在眼部钩端螺旋体滴度或钩端螺旋体PCR呈阳性的马中，与钩端螺旋体阴性眼睛相比，AH中IL-10（P = 0.0018；0.0032）和IP-10（P = 0.0342；0.043）显著升高。
抗炎细胞因子IL-10和促炎细胞因子IP-10似乎在ERU中起重要作用。需要进一步研究以进一步阐明和表征特定眼部炎症疾病的细胞因子谱，但多重珠免疫测定技术显示出作为有诊断价值工具的前景。
