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Tammie Lee Keadle, Norio Usui, Keith Andrew Laycock, Judith Kelvin Miller, Jay S. Pepose, Patrick Michael Stuart; IL-1 and TNF-α Are Important Factors in the Pathogenesis of Murine Recurrent Herpetic Stromal Keratitis. Invest. Ophthalmol. Vis. Sci. 2000;41(1):96-102.
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purpose. To better understand the role of interleukin (IL)-1 and tumor necrosis
factor (TNF)-α in recurrent herpetic stromal keratitis (HSK), the
cytokine content and the effects of anti-cytokine antibodies on mouse
corneas with the disease were examined.
methods. Competitive reverse transcription–polymerase chain reaction and
enzyme-linked immunosorbent analyses of IL-1α and TNF-α content
were performed on corneas removed 3, 5, 7, 10, 14, and 21 days after
latently infected NIH mice were irradiated with UV-B light to
reactivate herpes simplex virus (HSV). In separate experiments, mice
were injected with anti-IL-1 or anti-TNF-α antibodies 1 day before
and 7 days after reactivation.
results. UV-B irradiation stimulated an increase in corneal IL-1α mRNA in
reactivated (virus shedding) mice. This increase persisted longer and
was higher than in UV-B irradiated uninfected control animals. IL-1α
and TNF-α protein in corneas of reactivated mice was significantly
elevated on days 3 to 10 compared with day 0 levels, and exceeded
levels in control corneas on the same days. Anti-IL-1 and anti-TNF-α
antibody administration both resulted in significantly decreased
virus-induced corneal opacity between 7 and 21 days after UV-B
conclusions. IL-1α and TNF-α are upregulated in corneas in mice experiencing
recurrent HSK. Abrogation of virus-induced corneal disease by
anti-cytokine antibodies suggests that these cytokines play important
roles in the pathogenesis of recurrent disease. Therefore,
neutralization of specific proinflammatory cytokines may have potential
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