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

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. Corneas of BALB/c mice were transfected with plasmids expressing beta-galactosidase (beta-gal), IL-4, IL-10,...

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Published in:Graefe's archive for clinical and experimental ophthalmology 2006-02, Vol.244 (2), p.216-225
Main Authors: Bauer, Dirk, Lu, Mengji, Wasmuth, Susanne, Li, Haiping, Yang, Yanning, Roggendorf, Michael, Steuhl, Klaus Peter, Heiligenhaus, Arnd
Format: Article
Language:English
Subjects:
Administration, Topical
Animals
Antibodies, Viral - blood
Biolistics
Cornea - metabolism
Corneal Stroma - virology
Enzyme-Linked Immunosorbent Assay
Female
Gene Expression
Herpesvirus 1, Human - physiology
Hypersensitivity, Delayed - immunology
Immunologic Factors
Interleukin-10 - genetics
Interleukin-4 - genetics
Keratitis, Herpetic - genetics
Keratitis, Herpetic - immunology
Keratitis, Herpetic - prevention & control
Mice
Mice, Inbred BALB C
Ophthalmology
Plasmids - genetics
Transfection
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Summary: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. Corneas of BALB/c mice were transfected with plasmids expressing beta-galactosidase (beta-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. Expression of beta-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
ISSN:0721-832X
1435-702X
DOI:10.1007/s00417-005-0070-z