Cytokine expression in a rat model of Staphylococcus aureus endophthalmitis

PURPOSE. To examine the ability of viable Staphylococcus aureus to induce t he production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta , cytokine-induced neutrophil chemoattractant (CINC), and interferon (IFN)- gamma after intravitreal injection. METHODS. Experimental rat eyes were injected with a 25-mu l volume of appro ximately 80 colony-forming units of via ble S. aureus; control eyes receive d sterile saline. Eyes were graded daily for signs of clinical inflammation and were removed 6, 24, 48, and 72 hours after injection. One group was pr epared for histologic analysis, and vitreous was removed from the other gro up for cytokine analysis, using standard enzyme-linked immunosorbent assay procedures. RESULTS. TNF-alpha, IL-1 beta, CINC, and IFN-gamma were detected in experim ental vitreous samples at increased levels that peaked at 24 hours. TNF-alp ha, IL-1 beta, and CINC declined at 48 hours, but IFN-gamma remained elevat ed. At 72 hours, levels returned to baseline. Statistically significant ele vations of TNF-alpha, IL-1 beta, and CINC were detected in experimental sam ples at 24, but not at 6 and 48 hours compared with levels in saline contro l samples (P < 0.03). A statistically significant increase in IFN-gamma was detected at 24 and 48 hours compared with control levels (P < 0.03). In ex perimental animals, clinical inflammation and inflammatory cells peaked at 24 hours, persisted at 48 hours, and began to decline thereafter. Neutrophi ls were the predominant inflammatory cell detected at 24 (72.3% of cells) a nd 48 (60.1% hours. By 72 hours, the total number of inflammatory cells had decreased by 75.0%, and the cellular infiltrate had changed so that neutro phils equaled monocytes-macrophages. CONCLUSIONS. S. aureus induced the expression of TNF-alpha, IL-1 beta, CINC , and IFN-gamma. The time course of these cytokine levels could account for the clinical inflammatory responses and the entry and decline of vitreous cells in this model of bacterial endophthalmitis.