Cytokines are proteins produced by various cells in our body, including the immune system.
They have various functions, but when they are produced in excess - such as when the immune system is fighting an infection - they can cause significant damage to our body.
A team of researchers from across Australia and The Netherlands sought to better understand cytokine regulation and dysregulation when it comes to the body fighting an infection.
“With many respiratory viral infections, the seriousness is due in part to how the immune system responds to the infection,” co-author of the research Associate Professor Guna Karupiah, (pictured) from the Tasmanian School of Medicine, said.
“While the virus is growing and replicating and causes damage on its own, the immune system is also causing damage with the production of cytokines in response to the virus.
“Many cytokines are produced in high amounts when they are dysregulated, because the immune system is trying to fight the infection as hard as possible.”
Through using a mouse model of smallpox, the researchers focused on one cytokine, tumour necrosis factor (TNF), which is commonly produced as part of the inflammatory response to a viral infection.
The team sought to understand whether the absence of just one cytokine, TNF, could affect the production of other cytokines.
“Most cytokines are linked in some way to each other. So, if something goes wrong with one, it affects the production of another.
“Through our research we showed that deficiency in TNF, i.e. the absence of an inflammatory cytokine, paradoxically dysregulates other cytokines, worsens the inflammatory response and causes serious lung pathology.” Thus, in addition to being an inflammatory cytokine, TNF also plays an anti-inflammatory role.
Dr Karupiah said the study’s findings has the potential to better inform future treatments for respiratory viral infections. Dysregulated or excessive cytokine production, known as a “cytokine storm”, during a number of respiratory viral infections is associated with serious lung pathology
“For instance, we know that antivirals against influenza A viruses are only effective in the first 48 hours of the onset of symptoms,” he said.
“Typically, people don’t turn up to their GP until they are really ill, when it’s too late for the antivirals to have much impact.
“One of the reasons we believe the antivirals are not effective is because the immune system, with the dysregulation of cytokines, is also causing the damage.
“So, our current research shows that you can use the antiviral, after 48 hours, but it has to include a drug, targeting a cytokine that is produced in excess, to dampen inflammation.
“Currently this combination therapy against viral infections isn’t used, but we believe there is great potential.”
Dr Karupiah joined colleagues from local, national and international universities, including his wife Dr Geeta Chaudhri from the Australian National University, for the paper TNF deficiency dysregulates inflammatory cytokine production, leading to lung pathology and death during respiratory poxvirus infection.
The research was published in the Proceedings of the National Academy of Sciences of the United States of America.
