Abstract
BACKGROUND: 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. METHOD AND RESULTS: 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 Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus pneumoniae endophthalmitis had elevated levels of IL-1β, IL-6, IFN-γ, TNF-α, and IL-8, with earlier peaks observed in S. epidermidis 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. CONCLUSIONS: 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.