title: Tumor necrosis factor alpha small interfering RNA decreases herpes simplex virus-induced inflammation in a mouse model.
abstract: BACKGROUND
  Anti-TNFalpha antibodies have been used for treating inflammation in patients. But, more effective and safer drugs need to be developed for improved future therapeutic use.
  
  
  OBJECTIVE
  To inhibit the expression of TNFalpha, we used small interfering RNAs (siRNAs) to reduce over expression of TNFalpha in vitro in cell cultures and in an in vivo Behcet's disease-like (BD) mouse model for amelioration of chronic inflammation.
  
  
  METHODS
  TNFalpha siRNA was injected intraperitoneally twice with a 1-week interval. To compare the efficacy of TNFalpha siRNA versus an anti-TNFalpha antibody, Infliximab and Etanercept were administered to symptomatic mice with inflamed tissue.
  
  
  RESULTS
  Intraperitoneal delivery of TNFalpha siRNA effectively decreased BD symptoms in 18 of 32 cases (56.3%). Scrambled siRNA treatment decreased BD symptoms in 2 of 19 cases (10.5%). Infliximab was effective in 11 of 27 cases (40.7%) and Etanercept was also effective in 9 of 25 cases (36.0%) at the end of the second week after treatment. TNFalpha siRNA reduced serum levels of TNFalpha (1.57 +/- 0.43pg/ml), compared to levels in mice not injected (84.02 +/- 24.59pg/ml) (p<0.01) or scramble injected (118.89 +/- 20.08pg/ml) (p<0.01). After single injection of TNFalpha siRNA, improvement of BD symptoms showed at 9 +/- 7th day on an average, contrary, in Infliximab injected group, improvement was apparent at 15 +/- 4th day after injection (p<0.05).
  
  
  CONCLUSIONS
  We show that siRNAs can be employed to inhibit cytokine gene expression in an in vivo disease mouse model. This inhibition may, therefore, be attributed to the improvement of inflammatory symptoms.
authors.affiliation: Laboratory of Cell Biology, Ajou University Institute for Medical Sciences, Suwon, South Korea.
authors.forename: Bunsoon
authors.initials: B
authors.lastname: Choi
authors.forename: Yunchung
authors.initials: Y
authors.lastname: Hwang
authors.forename: Hyuk Jae
authors.initials: HJ
authors.lastname: Kwon
authors.forename: Eun-So
authors.initials: ES
authors.lastname: Lee
authors.forename: Kyung Sook
authors.initials: KS
authors.lastname: Park
authors.forename: Dongsik
authors.initials: D
authors.lastname: Bang
authors.forename: Sungnack
authors.initials: S
authors.lastname: Lee
authors.forename: Seonghyang
authors.initials: S
authors.lastname: Sohn
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D001528:Behcet Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D000068800:Etanercept; D007074:Immunoglobulin G / Q000494:pharmacology / Q000627:therapeutic use; D000069285:Infliximab; D008070:Lipopolysaccharides / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D034741:RNA, Small Interfering / Q000494:pharmacology / Q000627:therapeutic use*; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D018139:Simplexvirus / Q000472:pathogenicity*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D016207:Cytokines; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D034741:RNA, Small Interfering; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068800:Etanercept