A comparative study of the inhibitory effects of interleukin-1 receptor antagonist following administration as a recombinant protein or by gene transfer.

Anakinra, the recombinant form of IL-1 receptor antagonist (IL-1Ra), has been approved for clinical use in the treatment of rheumatoid arthritis as the drug Kineret trade mark, but it must be administered daily by subcutaneous injection. Gene transfer may offer a more effective means of delivery. In this study, using prostaglandin E2 production as a measure of stimulation, we quantitatively compared the ability of anakinra, as well as that of IL-1Ra delivered by gene transfer, to inhibit the biologic actions of IL-1beta. Human synovial fibroblast cultures were incubated with a range of doses of anakinra or HIG-82 cells genetically modified to constitutively express IL-1Ra. The cultures were then challenged with recombinant human IL-1beta either simultaneously with addition of the source of IL-1Ra or 24 hours later. In a similar manner, the potencies of the two sources of IL-1Ra were compared when human synovial fibroblasts were challenged with IL-1beta produced constitutively by genetically modified cells. No significant difference in inhibitory activity was observed between recombinant protein and IL-1Ra provided by the genetically modified cells, under static culture conditions, even following incubation for 4 days. However, under culture conditions that provided progressive dilution of the culture media, striking differences between these methods of protein delivery became readily apparent. Constitutive synthesis of IL-1Ra by the genetically modified cells provided sustained or increased protection from IL-1 stimulation over time, whereas the recombinant protein became progressively less effective. This was particularly evident under conditions of continuous IL-1beta synthesis.

The effect of metallic radial head arthroplasty on radiocapitellar joint contact area.

OBJECTIVE: This study determined the effect of metallic radial head arthroplasty on radiocapitellar joint contact area. DESIGN: The contact area of eight intact radiocapitellar joints was assessed during simulated compressive loading. Subsequently, the same experiments were repeated after reconstruction with three different radial head implant sizes. BACKGROUND: There has been an increasing use of metal radial head implants relative to silicone implants. However, the contact characteristics with the metal reconstruction have not been determined. METHODS: A 100 N compressive load was applied to the radiocapitellar joint at three different flexion angles for the native joint and three different sizes of a metal head implant. An impression material was employed to quantify joint contact area. RESULTS: Following metallic radial head arthroplasty, the contact area decreased by approximately two-thirds relative to the native radiocapitellar joint (P<0.001). Smaller implant sizes resulted in slightly larger contact areas (P<0.05). In addition, contact area decreased as joint flexion angle increased (P<0.04). CONCLUSIONS: Selection of radial head implant size is likely not a significant factor with regard to contact area mechanics of the radiocapitellar articulation. RELEVANCE: The effect of radial head implant size on the contact area produced with the native capitellum is not known. This study shows that the design or selection of a metallic radial head implant from the viewpoint of size is likely not an important factor with regard to minimizing joint contact stresses.