Research blast on... inflammation

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We know that inflammation is overactive in cystic fibrosis (CF), but we don’t understand what causes it to become overactive or how to reduce it. In this issue of Research Blast, we explain some of the questions that Trust-funded researchers are seeking to answer, from strategies to treat excess inflammation to ways of preventing it from becoming overactive in the first place.

Q How is managing inflammation like the zodiac sign Libra?

A It’s all a question of balance!

The first thing to say about inflammation is that it isn’t all bad! Inflammation helps defend the body from infections, and helps to minimise the impact of tissue damage. It is there because it can react quickly to things as they happen, such as fighting lung infections. One of its jobs is to call on other cells and chemicals in the body for help in managing the specific type of damage that has occurred. When more specialist help arrives, the body switches inflammation into ‘standby mode’. However, in CF, this ‘standby’ switch doesn’t work and so inflammation becomes overactive, causing tissue damage.

Scientists from our Innovation Hub on lung health at the University of Cambridge are investigating treatments for overactive inflammation in cystic fibrosis. Their remit is a tricky one, as they need to ensure there’s a good balance between keeping the important defensive activities of inflammation while reducing its overactive effects. This research could offer new hope for more effective, better tolerated anti-inflammatory drugs in the future.

Q How is CF inflammation like an over-sensitive smoke alarm?

A It’s easily triggered!

When the body is exposed to infection or tissue becomes damaged, a biological sensor recognises that something is wrong and triggers a series of processes in the rest of the cell, leading to inflammation. This sensor is called the ‘inflammasome’, and it can also be triggered when the cell is stressed.

Researchers have shown that the faulty CFTR protein in CF can cause an imbalance of salt in the cell, which the cell realises is abnormal so triggers the inflammasome sensor, when it otherwise wouldn’t be active. It’s a bit like an extremely sensitive smoke alarm that constantly goes off when the toast is burning or a candle is blown out!

Once this sensor is activated it can be hard to turn off, especially when infection is present, and this leads to overactive inflammation. Trust-funded researchers at the University of Leeds have recently shown that Orkambi and Symkevi can reduce the sensitivity of this sensor. This is the first time researchers have shown these drugs may have an anti-inflammatory effect in cystic fibrosis.

Q How are bugs in our gut like the US sitcom Friends?

A They’ll be there for you!

We constantly hear about how bacteria are bad for us, but that isn’t the whole picture. While some bacteria do cause infections, many other bacteria keep our bodies healthy and even fight off infection. We can find trillions (1,000,000,000,000s !) of these ‘good’ bacteria in our guts.

One of the most important things about the bacteria in our guts is that there is a good balance of the different types. Researchers have found in other conditions that an imbalance of bacteria (known as ‘dysbiosis’) in our gut could be contributing to inflammation in the body, including in our lungs. Potentially, this could be important in CF too, and researchers working in our ‘Gut dysbiosis’ Strategic Research Centre (SRC) are investigating the link between gut bacteria, lung function and inflammation in more detail.

To help the Trust fund vital research like this and support people with CF during the COVID-19 pandemic, make a donation today.

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