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1 From the Division of Ophthalmology, and the 2 Department of Pathology and Microbiology, University of Bristol, United Kingdom.
PURPOSE. To determine the pattern of cytokine production in the cornea and its relationship with viral antigens, in our murine model of recurrent ocular herpes simplex virus (HSV)-1 infection.
METHODS. Six weeks after corneal inoculation with HSV-1, the eyes of latently
infected and control mice were UV irradiated and examined for signs of
disease and viral reactivation. The eyes of five mice with recurrent
stromal disease and two controls were processed for
immunohistochemistry on days 4, 7, 10, and 14 after irradiation.
Sections were double stained for viral antigens and one of the
following cytokines: interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-10,
IL-12, and interferon (IFN)-
.
RESULTS. Fifty percent of mice showed signs of recurrent stromal disease, the
severity of which peaked on day 10 after UV irradiation. There was a
large cellular infiltrate in the stroma of all the corneas with
recurrent disease and the predominant cytokines were IL-1ß, IL-6,
IL-10, IL-12, and IFN-, all present in large numbers of cells on the
days studied. There were very few cells producing IL-2 and IL-4.
Control eyes had no significant cytokine-producing cells in the stroma.
CONCLUSIONS. These observations suggest that recurrent herpetic stromal keratitis
(HSK) may not be characterized by a classic T-helper (Th)1 or Th2
response. However, the large number of IFN-+ and
IL-12+ cells and the relative absence of IL-4 favors a Th1
response, and despite the numerous IL-10+ cells, the
overall balance of cytokine production appears to be proinflammatory.
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