Mutation offers Holy Grail to combat inflammation

The discovery of a human mutation that controls inflammation could lead to improved treatments for infectious diseases. Potentially, this could improve health outcomes worldwide for diseases such as bacterial infections, septic shock, or common colds and flu.

The mutation comes from a practical but little-known protein, Mal, and could help our immune system achieve the elusive ‘Goldilocks effect’, a response that is ‘not too hot, not too cold – but just right’.

When the immune system, our first line of defence, recognises infection, it produces inflammation to protect us from, then clear, the bacteria or virus. While inflammation is necessary, too much can lead to auto-immune disease or even death; while too little can result in an ineffective immune response, increasing disease and causing severe illness or even death.

A study from Associate Professor Ashley Mansell, published in the Journal of Immunology, shows targeting Mal would help the immune system deliver a balanced, optimal response.

    A/Prof Ashley Mansell

In the study, researchers were able to show that the mutation in Mal, found in fewer than three per cent of the population, can moderate inflammation. The inflammation produced in the preclinical model was reduced by around 50 per cent, but still provided the required response to infections such as influenza and E.coli.

“Looking at mutations like Mal could provide the basis of a therapeutic target to treat infectious diseases through producing a balanced inflammatory response.

“The perfect drug that targets inflammation will reduce, but not cut out, inflammation completely. This study suggests that through targeting Mal, this is a possibility,” A/Prof Mansell said.

Global potential

Infectious diseases range from common disorders such as sinusitis to a sore throat, through HIV infection and
Hepatitis B. They are a major global health concern.

Another positive health outcome could be for the treatment of sepsis, a potentially fatal condition caused by an overactive response to infection from the immune system. More than 15,000 cases of severe sepsis are recorded in Australia and New Zealand each year. Globally, sepsis affects up to 50 million people worldwide and causes 5.3 million deaths annually.

 

Collaborator: University of Massachusetts

 

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