title: High-level expression of interleukin-4 following electroporation-mediated gene transfer accelerates Type 1 diabetes in NOD mice.
abstract: Nonobese diabetic (NOD) mice develop T cell-dependent autoimmune disease. Administration of interleukin-4 (IL-4), one of the T helper 2 (Th2) cytokines, is reported to prevent either insulitis or diabetes or both in NOD mice. We examined the effect of transferring an IL-4-expressing plasmid vector into muscle by in vivo electroporation on the progression of diabetes in NOD mice. Plasmid DNA expressing murine IL-4 (pCAGGS-IL-4) was introduced into the muscles of 4- and 6-week-old female NOD mice using an in vivo electroporation technique we developed previously. The serum IL-4 levels reached 2000-8000 pg/ml 3 days after the delivery of pCAGGS-IL-4 and remained detectable (>5 pg/ml) for over 4 weeks. In contrast to the previous reports, 88% of the mice treated with pCAGGS-IL-4 developed overt diabetes by 30 weeks of age, while only 25% of nontreated mice and 19% of the mice treated with control pCAGGS developed overt diabetes by then (p<0.01). Therefore, highly expressed IL-4 introduced by in vivo electroporation may have caused a Th1 shift, resulting in the promotion of diabetes in NOD mice. The high serum concentration of cytokines attained by our method is likely to unveil previously unknown cytokine functions.
authors.affiliation: Division of Stem Cell Regulation Research (G6), Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, 565-0871, Osaka, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Horiki
authors.forename: Eiji
authors.initials: E
authors.lastname: Yamato
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Noso
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ikegami
authors.forename: Toshio
authors.initials: T
authors.lastname: Ogihara
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Miyazaki
mesh_terms: D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D004195:Disease Models, Animal; D018274:Electroporation; D018014:Gene Transfer Techniques; D007273:Injections, Intramuscular; D015847:Interleukin-4 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D010957:Plasmids / Q000008:administration & dosage
chemical_list: D015847:Interleukin-4