Tumor necrosis factor alpha small interfering RNA decreases herpes simplex virus-induced inflammation in a mouse model

SummaryBackgroundAnti-TNFα antibodies have been used for treating inflammation in patients. But, more effective and safer drugs need to be developed for improved future therapeutic use.ObjectivesTo inhibit the expression of TNFα, we used small interfering RNAs (siRNAs) to reduce over expression of TNFα in vitro in cell cultures and in an in vivo Behcet's disease-like (BD) mouse model for amelioration of chronic inflammation.MethodsTNFα siRNA was injected intraperitoneally twice with a 1-week interval. To compare the efficacy of TNFα siRNA versus an anti-TNFα antibody, Infliximab and Etanercept were administered to symptomatic mice with inflamed tissue.ResultsIntraperitoneal delivery of TNFα 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. TNFα siRNA reduced serum levels of TNFα (1.57 ± 0.43 pg/ml), compared to levels in mice not injected (84.02 ± 24.59 pg/ml) (p < 0.01) or scramble injected (118.89 ± 20.08 pg/ml) (p < 0.01). After single injection of TNFα 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).ConclusionWe 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.