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Updated: Aug 17, 2026
Ex Vivo Organotypic Corneal Model of Acute Epithelial Herpes Simplex Virus Type I Infection
Published on: November 3, 2012
Cytokine expression in murine corneas during recurrent herpetic stromal keratitis
T L Keadle1, N Usui, K A Laycock
1Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA.
Purpose:
Recurrent herpetic stromal keratitis (HSK) is a potentially blinding, immune-mediated disease. To better understand the immunopathology of recurrent HSK, we examined the cytokine profile of mouse corneas with the condition.
Methods:
The eyes of latently infected mice were examined for corneal pathology and cytokine content following UV-B-stimulated herpes simplex virus (HSV) reactivation.
Results:
Peak HSV-induced corneal disease, manifested by stromal opacification, occurred 7-14 days after viral reactivation in latently infected mice. In qualitative RT-PCR analyses, IFNgamma, IL-10, IL-4, and IL-12 p40 mRNA were simultaneously expressed before and during recurrent HSK. Competitive, semi-quantitative RT-PCR evaluation of cytokine mRNA revealed highest IFNgamma expression before and during clinical disease with a decline thereafter. IL-4 levels peaked and declined before day 14, while IL-10 peaked on days 7 or 14 and paralleled IFNgamma at lower levels. Small amounts of IL-12 p40 mRNA were detected late in the disease course. ELISA evaluation of corneal extracts demonstrated similar results, featuring early expression of Th2 cytokines relative to disease.
Conclusions:
The presence of Th2 cytokines during early stages of recurrent herpetic corneal lesions indicate the presence of a mixed Th1 and Th2 cell infiltrate, which is likely associated with a memory response to viral antigens. These data suggest that disease resolution in corneas with recurrent HSK may depend upon the balance between destructive and protective cytokines at individual sites of viral recurrence.
Insights
Recurrent herpetic stromal keratitis (HSK) involves a mixed Th1/Th2 immune response. Cytokine balance, particularly IFNgamma and IL-10, influences disease resolution in the cornea.
Area of Science:
- Immunology
- Ophthalmology
- Virology
Background:
- Recurrent herpetic stromal keratitis (HSK) is an immune-mediated corneal disease caused by herpes simplex virus (HSV).
- Understanding the immunopathology of HSK is crucial for developing effective treatments to prevent vision loss.
Purpose of the Study:
- To investigate the cytokine profile in mouse corneas during recurrent HSK.
- To elucidate the immunopathological mechanisms underlying HSK.
Main Methods:
- Latently HSV-infected mice were subjected to UV-B stimulation to induce viral reactivation.
- Corneal pathology and cytokine mRNA expression (IFNgamma, IL-10, IL-4, IL-12 p40) were analyzed using RT-PCR.
- Cytokine protein levels were quantified using ELISA.
Main Results:
- Recurrent HSK, characterized by stromal opacification, peaked 7-14 days post-reactivation.
- Simultaneous expression of IFNgamma, IL-10, and IL-4 mRNA was observed before and during disease.
- IFNgamma levels were highest during clinical disease, while IL-4 peaked early, and IL-10 paralleled IFNgamma at lower levels.
Conclusions:
- The early presence of Th2 cytokines suggests a mixed Th1/Th2 immune infiltrate during HSK.
- This mixed infiltrate is likely a memory response to HSV antigens.
- Disease resolution in HSK may depend on the balance of destructive and protective cytokines at recurrence sites.
