Abstract
Abstract: :
Purpose: We investigated the course of herpes simplex virus–1 stromal keratitis (HSK) and the corneal expression of TNF–α, IL–1 and IL–6 after local suppression of TNF–α with the use of antisense oligonucleotides (ASON). Methods: BALB/c mice were corneally infected with 105 PFU of HSV–1. The corneas were injected subepithelially with ASON targeting TNF–α on days –1, 1 and 4. Control groups of mice were treated with unrelated control oligonucleotides (CON), or with buffer or remained untreated. The animals were followed–up clinically for the signs of stromal keratitis. At day 14 post infection, the corneal cytokine content was analyzed by ELISA. The delayed–type hypersensitivity (DTH) reaction was tested, and the neutralizing antibody titers in the serum were determined by a plaque–assay. Results: 14% of the TNF–α ASON–treated mice, 62% of the untreated animals, 69% of the buffer treated ones and 41% of the CON–treated mice developed HSK. The corneal TNF–α–content of the ASON–treated mice was reduced when compared with the content detected in the HSV–, the buffer–treated or the CON–treated mice. The corneal IL–1–level of TNF–α ASON–treated mice was found to be lower than in the other groups. In parallel, the corneal content of IL–6 was diminished in the TNF–α–ASON treated mice. In contrast, the DTH and the neutralizing antibody titers did not differ between the groups. Conclusions: TNF–α ASON corneal treatment modulates the expression of pro–inflammatory cytokines in the cornea and improves the course of HSK, while the systemic anti–HSV immune response is not altered.
Keywords: cytokines/chemokines • herpes simplex virus • immunomodulation/immunoregulation