Table 1.
Selected in vivo studies targeting IL-1β, TNF-α and NF-κB for the treatment of OA.
| Target | Authors [Ref.] | Therapy | Type of study (model) | Main findings |
|---|---|---|---|---|
| IL-1β | ||||
| Pelletier et al [166] | IL-1Ra gene therapy | Pre-clinical (dogs) | Reduced lesion severity and progression | |
| Fernandes et al [167] | IL-1Ra gene therapy | Pre-clinical (rabbits) | Reduced lesion severity and progression | |
| Frisbie et al [168] | IL-1Ra gene therapy | Pre-clinical (horses) | Significant improvement in pain, disease activity and cartilage preservation | |
| Zhang et al [169] | IL-1Ra+IL-10 gene therapy | Pre-clinical (rabbits) | Significant reduction in cartilage breakdown | |
| Caron et al [170] | Recombinant IL-1Ra (Anakinra) | Pre-clinical (dogs) | Protection from OA lesions and reduction in collagenase-I expression | |
| Chevalier et al [171] | Recombinant IL-1Ra (Anakinra) | Clinical trial | Drug found to be safe and well-tolerated | |
| Chevalier et al [172] | Recombinant IL-1Ra (Anakinra) | Clinical trial | Not effective in relieving disease symptoms | |
| Bacconnier et al [173] | Recombinant IL-1Ra (Anakinra) | Case report (3 female patients) | Improvement in pain and global handicap in erosive OA of the hand | |
| TNF-α | ||||
| Grunke et al [174] | Monoclonal anti-TNF antibody (Adalimumab) | Case report (single 68 yr old male patient) | Relief from pain, improved movement and improved disease symptoms | |
| Magnano et al [175] | Monoclonal anti-TNF antibody (Adalimumab) | Pilot clinical trial (12 patients) | Well-tolerated, modest improvement in disease symptoms in erosive OA of the hand | |
| Fioravanti et al [176] | Monoclonal anti-TNF antibody (Infliximab) | Pilot clinical trial (10 female patients) | Well-tolerated and relief from pain but modest improvement in lesion in erosive OA of the hand | |
| NF-κB | ||||
| Hashimoto H et al [177] | NF-κB decoy oligodeoxynucleotde | Pre-clinical (rats) | Decrease in OA lesion (assessed by Mankin score), significant decrease in IL-1β and TNF-α levels in synovium and cartilage | |
| Chen et al [161] | Adenoviral vector-mediated NF-κBp65-specific siRNA | Pre-clinical (rats) | Reduced synovial inflammation, cartilage degradation and IL-1β and TNF-α levels in the synovium in early phase of experimental OA | |