Scientists at University College Dublin are trying to find ways to turn down the inflammation that arises with diseases such as arthritis, writes Claire O'Connell.
Sometimes the key to helping is knowing when to stop. In the body, inflammation plays an important role in counteracting injury. But if the body's emergency responses keep running unchecked, serious complications can arise.
That's why scientists at University College Dublin (UCD) want to tweak the body's own natural "stop signals" to help control inflammation more effectively and prevent it running amok.
"Every time we are injured the body has to have some sort of a response to defend itself against it," says Prof Pat Guiry, professor of synthetic organic chemistry at UCD and director of the Centre for Synthesis and Chemical Biology (CSCB).
"Even if you have a small cut you get accumulation of blood at the site of damage and you get the feeling of stiffness and swelling. Your body has to have some way of counteracting that, to clean up the process, initiate tissue repair and just get yourself back to working at 100 per cent."
As part of the inflammation process, white blood cells called neutrophils clean up debris from the injury site. "The neutrophils are like the emergency services, they get right to the site of action and absorb whatever has gone wrong with the damaged cells," explains Prof Guiry.
Normally, the body switches off these emergency services when the injury has been dealt with. But if for some reason the inflammation goes unregulated, it can cause problems, he says. "If inflammation doesn't stop, it can actually damage the tissue; it's bad news all round," he says, citing examples of conditions such as cystic fibrosis and rheumatoid arthritis where the body mounts a chronic, overactive inflammatory response.
One of the key stop signals for inflammation is a group of molecules called lipoxins, which the body makes itself. But the natural lipoxins are not ideal, because they break down quickly. "They have some shortcomings," he says. "Their potency is limited because the body breaks them down really quickly and that limits their activity."
So Prof Guiry's group decided to see whether they could tweak the chemical structures of some natural lipoxins to make them last longer and give them a better chance to be more biologically active. They identified key regions of the molecules and made minor changes in the lab, including sticking on a stabilising "aromatic ring" structure.
"If we are able to slow down the region where it is being metabolised, the biological activity might go up," says Prof Guiry, whose research group is funded by the Higher Education Authority and the science council, Ircset.
To test out the theory, they compared the effects of the natural and synthetic lipoxins on living cells in the lab. "As a chemist I have never been in favour of making compounds just for the sake of it that would sit in sample vials until I retired and then they were dumped," he states. "I am always keen they are tested in some way."
Working with Prof Catherine Godson, the group found that one of their synthetic lipoxins was more effective than its natural counterpart in turning down inflammation in cells. And the researchers are now looking at the potential anti-inflammatory effects of other interesting compounds that arose when they were synthesising the chemicals.
Ultimately the hope is to engineer more effective lipoxins that could be used as therapeutic agents against inflammation. "The experiments on the cells show us that we are on the right line," he notes. "And the synthetic chemistry approach we have developed is modular: we have three different bits that you add together so you can change any of those bits and you have a different molecule. It has opened a whole new vista of research for our group."