Locally administered lentivirus-mediated siRNA inhibits wear debris-induced inflammation in murine air pouch model.

Lentivirus(LV)-mediated small interfering RNA (siRNA) targeting tumor necrosis factor-alpha (TNF-alpha) was locally administered into the air pouch of mice to inhibit inflammation induced by titanium alloy particles. The lentiviral vector expressed green fluorescent protein (GFP) as a reporter gene. Down-regulation of TNF-alpha in pouch area was confirmed by real-time PCR and ELISA, resulting in significantly decreased local inflammatory responses (P < 0.01). This approach was proven safe by localized GFP fluorescence and invariant TNF-alpha expression in peripheral blood, liver, spleen, kidney, lung and brain of mouse. In conclusion, locally administered siRNA provides an effective and safe method for inhibiting particle-induced inflammation.