Supplementary Material for: Cytokine Expression in Staphylococcal and Streptococcal Endophthalmitis

<b><i>Background:</i></b> Endophthalmitis is an infection of ocular tissues, often with devastating outcomes for vision. Immunomodulation is an emerging avenue for therapeutic intervention in endophthalmitis, with the expression of cytokines central to potential mechanisms. This literature review with a systematic approach characterizes the cytokine expression in both animal and human staphylococcal and streptococcal endophthalmitis. <b><i>Method and Results:</i></b> Four online databases were searched for studies profiling cytokine levels in animal models or human populations with staphylococcal and/or streptococcal endophthalmitis. Of the 1,060 articles identified, 14 studies were included in this review comprising eight animal models and six human populations. Mouse, rat, and rabbit models of <i>Staphylococcus aureus</i>, <i>Staphylococcus epidermidis</i>, and <i>Streptococcus pneumoniae</i> endophthalmitis had elevated levels of IL-1β, IL-6, IFN-γ, TNF-α, and IL-8, with earlier peaks observed in <i>S</i>. <i>epidermidis</i> infection. Human endophthalmitis demonstrated significantly increased mediator levels compared to controls for a range of pro-inflammatory and anti-inflammatory cytokines, chemokines, and growth factors. Several associations were established between cytokine concentrations and both initial visual acuity and visual prognosis, with no consistent correlations across trials. <b><i>Conclusions:</i></b> It may be that virulence factors and the combinations of toll-like receptors activated influence the pathogen-specific visual outcomes observed in endophthalmitis. Furthermore, disease severity and potential therapeutic targets may be dependent on synergistic and compensatory cytokine pathways and the expression of anti-inflammatory mediators. Future research should aim to better characterize the roles of inflammatory mediators and solidify associations between pathogens, inflammation, and endophthalmitis outcomes. This has exciting implications for the prevention and treatment of endophthalmitis in clinical settings.

**背景：** 眼内炎（endophthalmitis）是指眼部组织的感染性炎症，常对视力造成毁灭性损害。免疫调节是眼内炎治疗领域新兴的干预方向，而细胞因子的表达是该治疗策略潜在机制的核心环节。本系统性综述旨在系统阐明动物模型及人类群体中葡萄球菌性与链球菌性眼内炎的细胞因子表达特征。

**方法与结果：** 本研究检索了4个在线数据库，筛选针对葡萄球菌和/或链球菌性眼内炎的动物模型或人类群体的细胞因子水平分析类研究。最终从1060篇检索文献中纳入14项符合标准的研究，其中包含8项动物模型研究与6项人群研究。针对金黄色葡萄球菌（*Staphylococcus aureus*）、表皮葡萄球菌（*Staphylococcus epidermidis*）及肺炎链球菌（*Streptococcus pneumoniae*）感染的小鼠、大鼠与兔模型研究显示，IL-1β、IL-6、IFN-γ、TNF-α及IL-8的水平均显著升高，且表皮葡萄球菌感染模型的细胞因子峰值出现更早。人类眼内炎患者的促炎细胞因子、抗炎细胞因子、趋化因子及生长因子水平较对照组均存在显著升高。多项研究证实细胞因子浓度与初始视力及视力预后存在关联，但各研究间未得到一致的相关性结果。

**结论：** 病原菌的毒力因子与激活的Toll样受体（Toll-like receptor）组合，可能是影响眼内炎病原体特异性视力结局的关键因素。此外，疾病严重程度与潜在治疗靶点可能依赖于协同与代偿性细胞因子通路及抗炎介质的表达模式。未来研究应进一步明确炎症介质的具体作用，巩固病原体、炎症反应与眼内炎结局之间的关联，这将为临床眼内炎的预防与治疗提供极具前景的思路。