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

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

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

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 exp ressing 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.

Original languageEnglish
Pages (from-to)216-225
Number of pages10
JournalGraefe's Archive for Clinical and Experimental Ophthalmology
Volume244
Issue number2
DOIs
StatePublished - Feb 2006
Externally publishedYes

Keywords

  • Antiviral defense
  • Cornea
  • Cytokine
  • Genegun
  • Herpetic stromal keratitis
  • Plasmid DNA
  • Topical particle-mediated administration

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