20 March 2013
Latest research from the Malaghan Institute of Medical Research reveals how a form of neutrophil cannibalism could help ease the symptoms of gouty arthritis.
Gout is one of the most painful forms of arthritis and is caused by the build-up of crystals of uric acid in and around the joints. The immune system reacts to the crystals as if they were viruses or bacteria, and it is the resulting inflammation that causes swelling, reddening of the skin and debilitating pain.
The prevalence of gout in New Zealand is twice that observed internationally, and it is three times more common in M?ori and Pacific populations.
For some individuals experiencing an acute attack of gout, their symptoms will improve over time, without the need for treatment.
We believe that understanding how and why gout inflammation spontaneously resolves in some situations will enable us to more quickly and effectively treat the disease, says Dr Jacquie Harper, Head of the Malaghan Institutes Arthritis & Inflammation research programme.
Her research, published this month in the international, peer-reviewed journal Arthritis & Rheumatism, has revealed that white blood cells called neutrophils could hold the key.
Neutrophils are one of the first inflammatory cells to respond to gout crystals. Part of the reason gout is so painful is because activated neutrophils release reactive oxygen species and bleach, which cause significant cell and tissue damage in the joints.
Previously thought to be primarily responsible for driving gout attacks, Dr Harper and PhD student Stefanie Steiger have now shown that neutrophils could also be part of a cure once they start eating each other that is!
We have known for some time that the spontaneous resolution of gout inflammation is associated with elevated levels of a protein called TGF-?1 in the synovial fluid of the affected joint, says Dr Harper. This protein is produced by many different cells, we were surprised to discover that neutrophils can produce it too.
Using a laboratory model of gout, Ms Steiger and Dr Harper showed that on contact with gout crystals, neutrophils release reactive oxygen species, and then die off. The dead neutrophils are then cleared by other neutrophils. This triggers the cells to produce TGF-?1, which minimises any further damage and shuts down inflammation.
Our research has revealed a novel mechanism that contributes to the controlled resolution of gout, says Dr Harper. We are now exploring different ways to target neutrophil cannibalism in the joints, so we can switch off inflammation at the very early stages of a gout attack, thus minimising the pain it causes.
This research was funded in part by the Wellington Medical Research Foundation.
Steiger S, Harper JL (2013) Neutrophil cannibalism triggers transforming growth factor ?1 production and self regulation of neutrophil inflammatory function in monosodium urate monohydrate crystal-induced inflammation in mice. Arthritis Rheum, 65:815-23.
Malaghan Institute Gout Researchers Stefanie Steiger and Dr Jacquie Harper.