New trigger for chronic inflammation in rheumatoid arthritis ...(are not effective for many patients. ....)

"We have uncovered one way that the immune system may be triggered to attack the joints in patients with rheumatoid arthritis. We hope our new findings can be used to develop new therapies that interfere with tenascin-C activation of the immune system and that these will reduce the painful inflammation that is a hallmark of this condition," added Dr Midwood.

The researchers reached their conclusions by carrying out five studies. One study suggested that tenascin-C was needed to sustain inflammation. The researchers induced joint inflammation in mice with and without the gene for tenascin-C. They found the mice that could produce tenascin-C had severe joint swelling with bone and cartilage destruction, but the mice that could not produce tenascin-C had no swelling or tissue destruction at all.

In a subsequent study, the researchers injected the active part of the tenascin-C molecule into mice joints. They found it caused the joints of the mice to become inflamed and that this reaction was more intense with higher doses.

Another experiment demonstrated that tenascin-C causes swelling in the joints by increasing levels of molecules that cause inflammation. The researchers took human immune cells called macrophages and cells called fibroblasts from the swollen joint of patients with rheumatoid arthritis and added tenascin-C. After the tenascin-C was added, the cells produced more molecules that cause inflammation.

The authors plan to work out the precise mechanism by which tenascin-C increases these levels of inflammatory molecules in the human joint and try to find ways to inhibit this action.

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