Using pCIN-mIL-4 DNA vector to express mRNA and protein and to improve herpes simplex virus-induced Behcet's disease symptoms in mice

Abstract

Behcet's disease (BD) is a chronic, recurrent, inflammatory, multisystemic disorder characterized primarily by vasculitis. The etiopathogenesis of BD involves immunogenetics, infectious organisms (streptococcus, herpes simplex virus), immunoregulation and vascular dysfunctions. We previously found that immunoregulation associated with viral infection was important to the development of BD-like symptoms. Recently, we demonstrated that Th2 cytokines up-regulated by Th2 adjuvant were efficient in attenuating or improving these BD-like symptoms. In order to directly augment IL-4 expression, a DNA vector (pCIN-mIL-4) was administered to BD-like mice using the Helios gene gun system. Two injections of the pCIN-mIL-4 vector, spread over 2 weeks, attenuated or improved the mucocutaneous symptoms of 10 out of 12 BD-like mice in our study. The improved mucocutaneous symptoms were crust in face, ulcer in mouth, scruff, back, genital and erythema. This improvement also correlated with induction of IL-4 mRNA in lymph nodes, protein in serum and intracellular IL-4 staining in splenocytes. Normal control mice (n = 10) injected with the pCIN-mIL-4 vector expressed IL-4 mRNA and showed more splenocytes stained with anti-IL-4 antibody (5.77 +/- 0.92%) than did mice injected with the pCIN control vector (3.34 +/- 0.25%; p = 0.02). These findings indicate that an IL-4 DNA vector could be used to express mRNA and protein in vivo and further suggest that such an IL-4 DNA vector could be used as a therapeutic treatment in recurrent inflammation shifted to T helper type 1 cytokine production.