Acetylsalicylic acid reduces viral shedding induced by thermal stress

Lions Eye Research Laboratories, LSU Eye Center, Louisiana State University Health Sciences Center, 2020 Gravier Street, New Orleans, LA 70112-2234, USA.
Current Eye Research (Impact Factor: 1.64). 08/2004; 29(2-3):119-25. DOI: 10.1080/02713680490504588
Source: PubMed


To investigate the effect of acetylsalicylic acid on ocular shedding of herpes simplex virus type 1 (HSV-1).
Mice that were latent for the McKrae strain of HSV-1 were treated with acetylsalicylic acid, a nonspecific inhibitor of cyclooxygenases, either prophylactically or at the time of heat stress-induced viral reactivation. The effect of the drug on viral shedding in the tear film, infectious virus in the cornea and trigeminal ganglion, and viral DNA in the cornea and trigeminal ganglion was determined.
Acetylsalicylic acid inhibited heat stress-induced shedding of virus in the tears and reduced the numbers of corneal and trigeminal ganglion homogenates containing virus. Intraperitoneal therapeutic and oral prophylactic plus therapeutic treatments were similar in their ability to inhibit reactivation.
The results indicate that a cyclooxygenase inhibitor such as acetylsalicylic acid can reduce recurrent viral infection in mice. These findings may implicate prostaglandins as agents in the viral reactivation process and suggest that therapy to suppress viral reactivation using nontoxic inhibitors of prostaglandin synthesis may be effective in humans.

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    • "Therefore, regulating the excessive immune response is crucial in controlling progressive visual impairment in recurrent HSK [2]. Previous reports have shown antiviral activity of a cyclooxygenase (COX) inhibitor against ocular infection with HSV-1 [4-6]. COX inhibitors, which belong to anti-inflammatory drugs, may contribute to controlling the massive immune response at an effective yet not deleterious level. "
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    ABSTRACT: 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-kappaB (NF-kappaB)-mediated mechanism in mice. 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-kappaB activation in the corneal tissues. The levels of tumor necrosis factor-alpha (TNF-alpha) in the cornea were determined by an enzyme-linked immunosorbent assay (ELISA). HSV-1 reactivation induced stromal edema and opacification concomitantly with elevated activation of NF-kappaB and elevated production of TNF-alpha. Lornoxicam treatment significantly decreased the incidence of recurrent HSK, attenuated the corneal opacity scores, and also effectively suppressed both NF-kappaB activation and TNF-alpha expression in biological analysis. Histopathology examination revealed a reduced immunostaining positive cell density for NF-kappaB in the cornea from lornoxicam-treated mice as well as a diminished inflammatory response. Lornoxicam exerts protective effects against HSK, presumably through the down-regulation of NF-kappaB activation.
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