Ending the perfect storm: Protein key to beating flu pandemics

A possible means of minimising the impact of flu pandemics

A protein called SOCS4 has been shown to act as a handbrake on the immune system’s runaway reaction to flu infection, providing a possible means of minimising the impact of flu pandemics.

Scientists from Melbourne’s Walter and Eliza Hall Institute have found that without SOCS4 the immune response to influenza infection is slowed and there is a vast increase in the number of damaging inflammatory molecules in the lungs. This flood of inflammatory molecules, known as a ‘cytokine storm’, is thought to contribute to flu-related deaths in humans.

Dr Lukasz Kedzierski, Dr Sandra Nicholson and colleagues from the institute, in collaboration with Associate Professor Katherine Kedzierska and colleagues from The University of Melbourne, made the discovery, which was published today in the journal PLOS Pathogens.

Suppressors of cytokine signalling (SOCS) molecules control the flow of chemical messages inside cells and were discovered by institute researchers in the 1990s. Immune cells release signalling molecules called cytokines to trigger an immune response that protects the body from infection. If too many cytokines are released, SOCS proteins suppress the activity of the cytokines to prevent unwanted inflammation and tissue damage.

Dr Kedzierski said removing SOCS4 upset the normal immune response to influenza infection. “We showed that, following influenza infection, the immune system did not respond as quickly as expected, and initially sent key immune cells to the wrong location in the body,” he said. “In addition, inflammatory cytokines began to accumulate in the lungs, leading to a cytokine storm that causes significant damage to the tissue.”

A cytokine storm could result in increased severity of symptoms and, in many instances, to multiple organ failure and death, Dr Kedzierski said. “A cytokine storm is like an uncontrolled chain reaction, and the cytokines that normally stimulate the immune response continue to trigger other immune cells to produce more cytokines. Our research suggests that SOCS4 keeps this response under control, preventing a cytokine storm in the lungs that can lead to a build up of fluid that restricts breathing and can ultimately result in death.”

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