Arthritis & Inflammation Group Current Research

Project One: Role of Macrophages and Monocytes in Acute Gouty Arthritis

Recruitment of immune cells called monocytes to the joints and connective tissues is a key characteristic of the inflammatory response observed in a variety of arthritic diseases.

In 2008 we published our pivotal finding that the resident macrophage is the key cell responsible for producing the initial inflammatory response to MSU, including the recruitment of damage-causing neutrophils that exacerbate the disease. In contrast, monocytes entering the site of inflammation contribute little to the initiation and early progression of inflammation induced by MSU crystals.

We are continuing to investigate the infiltrating monocyte populations in gouty arthritis to determine how their presence at the site of inflammation might be contributing to disease progression.

In other work we showed that the drug colchicine suppresses MSU-induced superoxide production by neutrophils in a murine model of gouty arthritis at sub-toxic doses. This is the first in vivo data to provide compelling support for the use of low dose, non-toxic, colchicine therapy for the treatment of gouty arthritis.

Project Two: A Clinical Study of Gouty Arthritis

Elevated levels of uric acid in the blood (hyperuricaemia) are a prerequisite for gout, however only 20 % of individuals with hyperuricaemia go on to develop gout and it is unclear why the other 80 % remain asymptomatic.

Three years ago we launched a clinical study to investigate whether immune cells isolated from patients with hyperuricaemia and/or gout, produce more inflammatory molecules compared with healthy subjects when exposed to the gout causing agent MSU crystals.

Our study has revealed significant differences in sensitivity to MSU crystal stimulation in gout patients compared with healthy individuals that might serve as a prognostic marker for developing the disease.

We are now in the final stages of data analysis and hope to publish the findings of this study in 2009.

Project Three: New Anti-inflammatory Treatments for Arthritis

In 2008 our anti-inflammatory research was recognised with the award of the prestigious Arthur E Schwarting Award for best paper published in the international Journal of Natural Products last year. The paper describes the discovery of two novel natural compounds from a sea squirt found in New Zealand's coastal waters that can inhibit acute inflammation.

This work represents the culmination of a joint venture, TerraMarine Pharmaceuticals, that was formed in 2002 between the Malaghan Institute, Crop and Food Research, The University of Auckland and the National Institute of Water and Atmospheric Research, to screen New Zealand's unique plant and marine life for novel bioactive compounds.

This work is underpinned by a patent application around the structure and application of these compounds for the treatment of arthritis and other inflammatory diseases involving neutrophils.

We are also involved in an ongoing collaboration with HortResearch to develop anti-inflammatory neutraceuticals for improving the management of inflammatory conditions.

 

Collaborators

Assoc Prof Brent Copp, The University of Auckland, New Zealand

Prof Carolyn Geczy, University of New South Wales, Sydney, Australia

Dr Andrew Harrison, University of Otago - Wellington School of Medicine, New Zealand

Dr Roger Hurst, HortResearch Ruakura, Hamilton, New Zealand

Dr Stephen Geiseg, University of Canterbury, New Zealand

Dr Keryn Johnson, Industrial Research Limited, Lower Hutt, New Zealand

Dr Nigel Perry, Crop and Food Research, New Zealand

Dr Vicky Webb, NIWA, New Zealand

Dr Antony Wheatley, University of Otago, New Zealand

 

Funding Sources

Arthritis New Zealand

Foundation for Research, Science & Technology

Health Research Council of New Zealand

New Zealand Lottery Health Research

Nikau Foundation (previously Wellington Region Foundation)

Wellington Medical Research Foundation