New research recently published in the American Journal of Respiratory and Critical Care Medicine details the discovery of an immune signature that may predict whether patients who have been newly diagnosed with influenza are likely to develop severe symptoms and experience poor outcomes.
The research team, led by Investigators from St. Jude Children's Research Hospital in Tennessee, says the findings could also help explain why young children have a higher risk of complications as a result of influenza.
For the study, which is still ongoing, the researchers analyzed 84 individuals with influenza that had been acquired from the community.
Participants were aged between 3 weeks and 71 years, and 41 of the participants were children aged 23 months or younger.
The investigators collected blood, nasal swabs and nasal wash samples from all participants and used these to track their flu infection and immune responses to it for 28 days.
The first set of samples was taken once patients sought medical attention for their flu symptoms, and sampling was repeated on days 3, 7, 10 and 28.
The investigators carried out similar sampling on 126 volunteers from the households of the flu patients.
The researchers also measured the levels of 42 cytokines - small proteins important to cell signaling - in each participant as well as the levels of antibodies that worked against the circulating flu virus.
Children have more aggressive inflammatory response to flu
The researchers found that both children and adults were able to eliminate the virus from their bodies in 7-10 days.
But from analyzing cytokines levels in the blood, nose and sinuses, the researchers found that children had a much more aggressive inflammatory response to influenza compared with adults - a finding the investigators were not expecting to see.
Christine Oshansky, of St. Jude Children's Research Hospital and first author of the study, says:
"The fact that the innate immune response was stronger in the airways of children than adults was a surprise. Previous studies using different measures reported that children mounted a weaker immune response."
The investigators say this finding could explain why infants and toddlers are more likely to suffer severe flu symptoms.
High levels of three cytokines 'predicts severe flu symptoms'
Looking into the inflammatory response further, the researchers discovered that high levels of three cytokines at flu diagnosis - MCP-3, interferon alpha 2 (IFNa2) in the nasal and interleukin-10 (IL-10) in the blood - predicted the occurrence of severe flu symptoms later.
Furthermore, the investigators found that patients with high blood levels of IL-10, MCP-3 and interleukin-6 were more likely to be hospitalized as a result of their influenza symptoms.
Researchers found that infants and toddlers have a more aggressive inflammatory response to influenza compared with adults, which could explain why children are more likely to suffer severe flu symptoms.
According to the researchers, MCP-3 and IFNa2 trigger inflammation, while IL-10 curbs inflammation. They note that high IL-10 levels usually mean that the body is attempting to switch off the inflammatory response.
Additionally, the investigators found that inflammatory cytokine levels were associated with monocytes - white blood cells - that are called to infection sites.
The researchers explain that different types of monocytes can trigger a variety of immune responses through cytokine secretion. They note that although some of these inflammatory responses can be beneficial, some of them could hamper the recovery of the patient.
Overall, the investigators say it is clear that new treatments need to be created that target this immune signature.
Paul Thomas, of the Department of Immunology at St. Jude Children's Research Hospital and co-author of the study, says:
"Patients in this study could handle the flu virus and clear it from their lungs in a week to 10 days. The problem for patients with this immune signature is likely the inflammatory environment in their airways created by the innate immune system in response to the virus.
Clinically, we need to explore targeted therapies to address this problem separately from efforts to clear the virus."
The findings could also explain why the beneficial effects of antiviral drug oseltamivir quickly fade out in the early stages of flu.
"This drug helps get rid of the virus, but these patients do not appear to have a problem with that," adds Thomas.
Last year, Medical News Today reported on a study suggesting that the flu virus is able to wipe out the immune system's primary defense against virus re-infection.