IL-1 and TNF-alpha are important factors in the pathogenesis of murine recurrent herpetic stromal keratitis.
OBJECTIVE
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.
Keadle
T L
TL
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, USA.
Usui
N
N
Laycock
K A
KA
Miller
J K
JK
Pepose
J S
JS
Stuart
P M
PM
D000818:Animals; D003319:Corneal Stroma / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D017931:DNA Primers / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018259:Herpesvirus 1, Human / Q000254:growth & development; D007074:Immunoglobulin G / Q000008:administration & dosage; D007375:Interleukin-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016849:Keratitis, Herpetic / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D051379:Mice; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000378:metabolism; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation; D014775:Virus Activation / Q000528:radiation effects; D017201:Virus Shedding / Q000502:physiology
D017931:DNA Primers; D007074:Immunoglobulin G; D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha