Arthritis & Inflammation Group Current Research
Project One: Role of Macrophages and Monocytes in Acute Gouty Arthritis
A key characteristic of the inflammatory response observed in a variety of arthritic diseases is the recruitment of immune cells called monocytes to the joints and connective tissues. These cells have the potential to develop into either proinflammatory or anti-inflammatory macrophages and might therefore either contribute to inflammation or shut it down respectively.
Last year we showed that monocytes entering the site of inflammation contributed little to the initiation and early progression of inflammation induced by MSU crystals. In 2007 we have gone on to successfully identify the resident macrophage as the key cell responsible for producing the initial inflammatory response to MSU, including the recruitment of damage-causing neutrophils that exacerbate the disease. We also found that whereas macrophages recruit neutrophils in response to MSU, epithelial cells recruit monocytes. The significance of this finding for disease therapy with respect to the potential to target different arms of inflammation in gout is the subject of current investigation.
We are also 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.
Project Two: A Clinical Study of Gouty Arthritis
Monocyte and neutrophil recruitment is a key characteristic of the inflammatory response to MSU in gout patients. For this reason they are the cellular targets of our clinical study into gouty arthritis.
Interestingly, only 20 % of people with elevated levels of uric acid in the blood develop gout, and it is unclear why the other 80 % remain asymptomatic.
The clinical study aims to determine whether immune cells isolated from the blood of healthy volunteers and gout patients respond differently to MSU and whether these responses correlate with susceptibility to or protection from developing gout.
The clinical study is now in year two and we have recruited half of the participants and some of our interim data has already revealed interesting differences between the inflammatory responses of different gout patient groups and healthy controls.
This work complements our basic research programme investigating the mechanisms of inflammation during the early onset of arthritis and will be presented at a major international clinical rheumatology conference in 2008.
Project Three: New Anti-inflammatory Treatments for Arthritis
TerraMarine Pharmaceuticals, a joint venture comprising the MIMR, Crop and Food Research (CFR) and the National Institute of Water and Atmospheric Research (NIWA), has now identified lead compounds from a New Zealand sponge that both inhibits neutrophil activation and suppresses neutrophil infiltration in gouty inflammation. These compounds have now undergone extensive structure-activity studies allowing us to identify the optimal structure(s) for specific anti-inflammatory activity and future drug development.
This work is underpinned by protection of the intellectual property around the structure and application of these compounds for the treatment of arthritis and other inflammatory diseases involving neutrophils.
In 2007 we also initiated a collaboration with HortResearch to develop anti-inflammatory neutraceuticals for improving management of inflammatory conditions.
Clinical Relevance and Future Direction
Over the coming years we would like to expand our basic research programme to include other arthritic and inflammatory diseases.
We would also like to develop a greater interface with the clinic to set up more clinical trials into inflammatory disease.
Finally, we hope to be able to use our basic research findings to identify new targets for disease therapy that can be taken into drug development.
Collaborators
Assoc Prof Brent Copp, Auckland University, New Zealand
Prof Carolyn Geczy, University of New South Wales, Sydney, Australia
Dr Andrew Harrison, Wellington School of Medicine, New Zealand
Dr Roger Hurst, HortResearch Ruakura, Hamilton, 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
