Inflammation – a hot topic
What do you think when you hear the word ‘inflammation’? Redness and heat? The bodily response to injury or infection is aptly named, and it’s currently a hot topic in the world of biomedicine.
That’s because it’s becoming apparent that inappropriate inflammation goes hand in glove with many different medical conditions - some acute like serious complications of infection, and some chronic such as cancer, arthritis, some neurodegenerative diseases and even obesity.
New approaches are now being developed and tested to tone down inflammation that has run amok - and selectively switching off inflammatory triggers that are causing trouble in the body could hold the key to better treatment of many diseases and conditions.
Inflammation wasn’t always so hot, explains SFI-funded researcher Luke O’Neill, professor of biochemistry at Trinity College Dublin.
He describes how for a long time the field of immunology – which looks at how the body fights infection – was focused on how we ‘remember’ diseases we have encountered before, looking at the complex interplay of cell types within the immune system.
In this context, inflammation, with all its increased blood flow, was seen as a means of getting immune cells in place in the body to do their job.
But in the 1980s, discoveries at the molecular level showed that inflammation had more subtle and intriguing roles: inflammatory cells were making molecules to help to activate the cells that help us fight infection, notes Prof O’Neill.
Then in the 1990s, the discovery of biochemical receptors on immune cells called Toll-like receptors (TLRs) shifted the whole field on its axis, he adds.
TLRs have now been identified as a mechanism by which immune cells ‘see’ invaders like bacteria, but they have also been implicated in triggering inappropriate inflammation in a range of medical conditions.
Prof O’Neill was among the first researchers in the world to work on TLRs, and his SFI-funded research led to the formation of a company, Opsona Therapeutics. The spin-out has now developed specific antibodies to switch off troublesome TLRs in the body, particularly homing in on auto-immune conditions like rheumatoid arthritis as well as organ transplantation.
The field has come a long way since Prof. O’Neill came back to Ireland in the 1990s. At that time he found other immunologists here – notably Prof. Kingston Mills and Prof. Cliona O’Farrelly – were working on complementary aspects of the immune system.
Together they started to build up research teams, and the efforts are paying off. Thomson Reuters recently ranked Ireland third in the world for the quality of scientific publications in immunology between January 1999 and October 2009.
“That third in the world statistic is great - it shows that in the area we are successful, we have labs that are punching above their weight internationally,” says Prof. O’Neill.
“And why is that? It’s a bit of a coincidence that several of us came back to Ireland and set up labs and were good in our fields. We happen to be well placed in Ireland to ask the questions and get answers to them, and SFI came along at exactly the right time [early 2000s] for us to realise our ambitions and do the research we wanted to do. Without that money we would have been struggling to get the funds.”
Prof O’Neill also explains that on a wider level, thanks to the advent of molecular techniques and the availability of patient samples, immunology and the control of wayward inflammation have become particularly fertile areas of research.
“There are three big pillars of biomedical research: cancer, neurobiology and immunology,” he says. “In the past 20 years immunology has outstripped the other two, and one of the reasons is that it is more tractable. The major diseases, things like rheumatoid arthritis, diabetes, psoriasis, multiple sclerosis, there is no question about this but we are all convinced these diseases are really tractable now. If you go forward five or 10 years we can be confident that there will be major treatments for those diseases.”
