IL-1 and TNF-alpha are important factors in the pathogenesis of murine recurrent herpetic stromal keratitis.

Abstract

PURPOSE:

To better understand the role of interleukin (IL)-1 and tumor necrosis factor (NF)alpha 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-1alpha and TNF-alpha 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-a antibodies 1 day before and 7 days after reactivation.

RESULTS:

UV-B irradiation stimulated an increase in corneal IL-la mRNA in reactivated (virus shedding) mice. This increase persisted longer and was higher than in UV-B irradiated uninfected control animals. IL-1alpha and TNF-alpha 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-alpha antibody administration both resulted in significantly decreased virus-induced corneal opacity between 7 and 21 days after UV-B exposure.

CONCLUSIONS:

IL-1alpha and TNF-alpha 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 therapeutic value.

• Authors: T L Keadle, N Usui, K A Laycock, J K Miller, J S Pepose, P M Stuart
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 41 Issue 1 Pg. 96-102 (Jan 2000) ISSN: 0146-0404 [Print] United States
• PMID: 10634607 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• DNA Primers
• Immunoglobulin G
• Interleukin-1
• RNA, Messenger
• Tumor Necrosis Factor-alpha

Topics

• Animals
• Corneal Stroma (metabolism, pathology, virology)
• DNA Primers (chemistry)
• Enzyme-Linked Immunosorbent Assay
• Female
• Herpesvirus 1, Human (growth & development)
• Immunoglobulin G (administration & dosage)
• Interleukin-1 (genetics, immunology, metabolism)
• Keratitis, Herpetic (etiology, metabolism, pathology, virology)
• Mice
• Mice, Inbred Strains
• RNA, Messenger (metabolism)
• Recurrence
• Reverse Transcriptase Polymerase Chain Reaction
• Tumor Necrosis Factor-alpha (genetics, immunology, metabolism)
• Up-Regulation
• Virus Activation (radiation effects)
• Virus Shedding (physiology)