Cytokine expression in a rat model of Staphylococcus aureus endophthalmitis.

PURPOSE: To examine the ability of viable Staphylococcus aureus to induce the production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, cytokine-induced neutrophil chemoattractant (CINC), and interferon (IFN)-gamma after intravitreal injection.

METHODS

Experimental rat eyes were injected with a 25-microl volume of approximately 80 colony-forming units of viable S. aureus; control eyes received 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 prepared for histologic analysis, and vitreous was removed from the other group for cytokine analysis, using standard enzyme-linked immunosorbent assay procedures.

RESULTS

TNF-alpha, IL-1beta, CINC, and IFN-gamma were detected in experimental vitreous samples at increased levels that peaked at 24 hours. TNF-alpha, IL-1beta, and CINC declined at 48 hours, but IFN-gamma remained elevated. At 72 hours, levels returned to baseline. Statistically significant elevations of TNF-alpha, IL-1beta, and CINC were detected in experimental samples at 24, but not at 6 and 48 hours compared with levels in saline control 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 experimental animals, clinical inflammation and inflammatory cells peaked at 24 hours, persisted at 48 hours, and began to decline thereafter. Neutrophils were the predominant inflammatory cell detected at 24 (72.3% of cells) and 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 neutrophils equaled monocytes-macrophages.

CONCLUSIONS

S. aureus induced the expression of TNF-alpha, IL-1beta, 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.