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Modulation of viral immunoinflammatory responses with cytokine DNA administered by different routes
S Chun1, M Daheshia, N A Kuklin
1Department of Microbiology, University of Tennessee, Knoxville, Tennessee 37996-0845, USA.
Abstract:
The efficacy of plasmid DNA encoding cytokine administered by different routes, systemic or surface exposure, was evaluated and compared for their modulating effects on subsequent lesions caused by infection with herpes simplex virus (HSV). Systemic or topical administration of both interleukin-4 (IL-4) and IL-10 DNA but not IL-2 DNA caused a long-lasting suppression of HSV-specific delayed-type hypersensitivity response. IL-4 or IL-10 DNA preadministration also modulated the expression of immunoinflammatory lesions associated with corneal infection of HSV. Suppression of ocular lesions required that the DNA be administered to the nasal mucosa or ocular surfaces and was not evident after intramuscular administration. The modulating effect of IL-10 DNA was most evident after topical ocular administration, whereas the effects of IL-4 DNA given by both routes appeared to be equal. Preexposure of IL-4 DNA, but not IL-10 DNA, resulted in a significant change in Th subset balance following HSV infection. Our results indicate that the modulating effect of IL-4 or IL-10 DNA may proceed by different mechanisms. Furthermore, our results suggest that surface administration of cytokine DNA is a convenient means of modulating immunoinflammatory lesions.
Insights
Administering plasmid DNA encoding interleukin-4 (IL-4) or interleukin-10 (IL-10) suppressed herpes simplex virus (HSV) lesions. Surface delivery of cytokine DNA offers a convenient method for modulating immunoinflammatory responses.
Area of Science:
- Immunology
- Virology
- Gene Therapy
Background:
- Herpes simplex virus (HSV) infections can cause significant immunoinflammatory lesions.
- Modulating immune responses is crucial for managing viral infections.
- Cytokine gene therapy offers a potential strategy for immune modulation.
Purpose of the Study:
- To evaluate and compare the efficacy of plasmid DNA encoding cytokines (IL-4, IL-10, IL-2) administered via systemic or surface routes for modulating HSV-induced lesions.
- To investigate the impact of different administration routes on the suppression of HSV-specific immune responses and ocular lesions.
- To elucidate potential differences in the mechanisms of action for IL-4 and IL-10 DNA in modulating HSV infection.
Main Methods:
- Plasmid DNA encoding interleukin-4 (IL-4), interleukin-10 (IL-10), or interleukin-2 (IL-2) was administered systemically or topically.
- Mice were subsequently infected with herpes simplex virus (HSV).
- HSV-specific delayed-type hypersensitivity responses and ocular lesion development were assessed.
Main Results:
- Systemic or topical administration of IL-4 DNA and IL-10 DNA, but not IL-2 DNA, suppressed HSV-specific delayed-type hypersensitivity.
- IL-4 or IL-10 DNA preadministration modulated HSV-associated immunoinflammatory ocular lesions.
- Suppression of ocular lesions was dependent on surface administration (nasal or ocular), not intramuscular.
- IL-10 DNA showed maximal effect with topical ocular administration; IL-4 DNA effects were similar via both routes.
- IL-4 DNA preexposure altered Th subset balance post-HSV infection, unlike IL-10 DNA.
Conclusions:
- Modulating effects of IL-4 and IL-10 DNA on HSV infection may involve distinct mechanisms.
- Surface administration of cytokine DNA is a practical approach for managing immunoinflammatory lesions.
- Cytokine gene therapy holds promise for controlling herpes simplex virus infections.