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Graefe's Archive for Clinical and Experimental Ophthalmology

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01-02-2006 | Laboratory Investigation

Immunomodulation by topical particle-mediated administration of cytokine plasmid DNA suppresses herpetic stromal keratitis without impairment of antiviral defense

Authors: Dirk Bauer, Mengji Lu, Susanne Wasmuth, Haiping Li, Yanning Yang, Michael Roggendorf, Klaus Peter Steuhl, Arnd Heiligenhaus

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 2/2006

Abstract

Background

We investigated whether the course of herpetic stromal keratitis (HSK) in BALB/c mice could be altered by topical gene-gun-mediated administration of interleukin (IL)-4 or IL-10 plasmid DNA.

Methods

Corneas of BALB/c mice were transfected with plasmids expressing β-galactosidase (β-gal), IL-4, IL-10, granulocyte-macrophage colony-stimulating factor (GM-CSF), and pCR3.1 (control) 2 days before Herpes simplex virus-1 (HSV-1; KOS) infection. Development of keratitis and cell infiltration were studied. HSV-1 replication was monitored by plaque assay. Expression of cytokines was detected by enzyme-linked immunosorbent assay. HSV-specific proliferation in the regional lymph nodes and spleens was measured. HSV-1 neutralizing antibody titers and IgG2A/IgG1 ratios were determined.

Results

Expression of β-gal was found in the treated corneas, but not in other tissues. IL-4 or IL-10 plasmid administration induced cytokine production in the corneas. After treatment with 300 psi, the severity of HSK was attenuated (each P<0.05), and the numbers of infiltrating inflammatory cells were lower than in the pCR3.1-treated controls (P<0.001). IL-6, but not IL-1α, expression in the cornea was reduced after treatment with IL-4 or IL-10 plasmid DNA. The HSV-1-specific DTH response, corneal Th1 cytokine profile, IgG/IgG2a/IgG1 ratio, neutralizing antibody titers, and virus clearance did not differ between the groups.

Conclusions

Thus, topically administered IL-4 and IL-10 plasmid DNA can lead to a milder course of HSK without impeding viral clearance. The gene gun technique for corneal delivery of plasmid cytokine DNA may be useful for modulating local immune responses without affecting antiviral defense.

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Title: Immunomodulation by topical particle-mediated administration of cytokine plasmid DNA suppresses herpetic stromal keratitis without impairment of antiviral defense
Authors: Dirk Bauer
Mengji Lu
Susanne Wasmuth
Haiping Li
Yanning Yang
Michael Roggendorf
Klaus Peter Steuhl
Arnd Heiligenhaus
Publication date: 01-02-2006
Publisher: Springer-Verlag
Published in: Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 2/2006
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI: https://doi.org/10.1007/s00417-005-0070-z

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Immunomodulation by topical particle-mediated administration of cytokine plasmid DNA suppresses herpetic stromal keratitis without impairment of antiviral defense

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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