Modulation of Viral Immunoinflammatory Responses with Cytokine DNA Administered by Different Routes

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.

本研究评估并比较了经不同给药途径（全身给药或表面暴露）递送的编码细胞因子的质粒DNA（plasmid DNA）的效力，及其对单纯疱疹病毒（herpes simplex virus, HSV）感染所引发后续损伤的调节作用。仅白细胞介素4（interleukin-4, IL-4）与白细胞介素10（IL-10）的DNA，而非白细胞介素2（IL-2）DNA，经全身或局部给药后，可长期抑制HSV特异性迟发型超敏反应（delayed-type hypersensitivity response）。提前给予IL-4或IL-10 DNA，还可调节HSV角膜感染相关免疫炎性损伤的表达。抑制眼部损伤需将DNA施用于鼻粘膜或眼表，经肌内给药后则未观察到该抑制效应。IL-10 DNA的调节作用在眼部局部给药时最为显著，而两种给药途径下IL-4 DNA的调节效果相当。提前给予IL-4 DNA（而非IL-10 DNA）可使HSV感染后的T辅助细胞亚群平衡发生显著改变。本研究结果表明，IL-4或IL-10 DNA的调节作用可能通过不同机制实现。此外，本研究结果提示，细胞因子DNA的表面给药是一种便捷的调节免疫炎性损伤的手段。