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.