Lornoxicam suppresses recurrent herpetic stromal keratitis through down-regulation of nuclear factor-κB: an experimental study in mice

PURPOSE: We designed the current study to determine the protective effects of lornoxicam, a cyclooxygenase (COX) inhibitor, on recurrent herpetic stromal keratitis (HSK) and the nuclear factor-κB (NF-κB)-mediated mechanism in mice. METHODS: A corneal latent herpes simplex virus-1 (HSV-1) infected mouse model was established. Six weeks later, Ultraviolet B (UVB) irradiation induced the recurrence. Corneal swabs were obtained and cultured with indicator cells to determine shedding of the virus. Lornoxicam was administered intraperitoneally daily, beginning one day before irradiation and lasting for seven days. Saline-treated and mock-infected control groups were also studied at the same time. Development of corneal inflammation and opacity was scored. Immunohistochemical staining and an electrophoretic mobility shift assay were performed to evaluate the effect of lornoxicam on NF-κB activation in the corneal tissues. The levels of tumor necrosis factor-α (TNF-α) in the cornea were determined by an enzyme-linked immunosorbent assay (ELISA). RESULTS: HSV-1 reactivation induced stromal edema and opacification concomitantly with elevated activation of NF-κB and elevated production of TNF-α. Lornoxicam treatment significantly decreased the incidence of recurrent HSK, attenuated the corneal opacity scores, and also effectively suppressed both NF-κB activation and TNF-α expression in biological analysis. Histopathology examination revealed a reduced immunostaining positive cell density for NF-κB in the cornea from lornoxicam-treated mice as well as a diminished inflammatory response. CONCLUSIONS: Lornoxicam exerts protective effects against HSK, presumably through the down-regulation of NF-κB activation.