Interleukin-6 small interfering RNA improved the herpes simplex virus-induced systemic inflammation in vivo Behcet's disease-like mouse model.
It is known that the level of interleukin-6 (IL-6) is higher in patients with active Behcet's disease (BD) than in those with inactive disease. Herpes simplex virus (HSV) type 1 inoculation of the earlobes of ICR mice resulted in the development of BD-like symptoms. To find out whether downregulation of IL-6 would affect the symptoms of BD, IL-6 small interfering RNA (siRNA) was administered to a BD mouse model. IL-6 siRNA was intraperitoneally injected into BD mice to downregulate IL-6 (n=9). IL-6 siRNA injection downregulated serum IL-6 level (118.9+/-114.4 pg ml(-1)) compared with scramble injection (439.4+/-378.0 pg ml(-1)) in BD mice (P=0.01). In seven out of nine IL-6 siRNA-injected BD mice, 77.8% improved and the severity score was decreased from 3.1+/-1.05 to 1.7+/-0.87 (P=0.005), whereas two out of six (33.3%) scramble-injected BD mice improved and the severity score changed from 2.5+/-0.84 to 2.0+/-1.41 (P=0.203). Foxp3, ROR gamma t, IL-17A, IL-17F and tumor necrosis factor-alpha were also influenced in IL-6 siRNA-injected BD mice compared with scramble-injected BD mice. Adoptive transfer of CD4+CD25+ cells to BD mice affected the decrease of IL-6 serum levels and were dependent on CD4+CD25+ cell numbers. These results showed that downregulation of IL-6 improved the inflammatory symptoms in BD mice through upregulation of regulatory T cells and inhibition of Th17 cells.
Shim
J
J
Laboratory Cell Biology, Institute for Medical Sciences, Ajou University, Suwon, Korea.
Byun
H O
HO
Lee
Y D
YD
Lee
E S
ES
Sohn
S
S
D019264:Adoptive Transfer; D000818:Animals; D001528:Behcet Syndrome / Q000235:genetics / Q000276:immunology / Q000628:therapy* / Q000821:virology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D015316:Genetic Therapy / Q000379:methods*; D006561:Herpes Simplex / Q000150:complications*; D018259:Herpesvirus 1, Human; D020381:Interleukin-17 / Q000096:biosynthesis; D053759:Interleukin-23 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D034622:RNA Interference / Q000276:immunology; D034741:RNA, Small Interfering / Q000235:genetics*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000097:blood; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D020381:Interleukin-17; D053759:Interleukin-23; D015850:Interleukin-6; D034741:RNA, Small Interfering; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha