IL-27 balances the immune response to influenza and reduces lung damage

May 8, 2014
This is a colorized EM picture of a budding influenza virus in human lung tissue. Credit: RKI colleagues Gudrun Holland and Michael Laue, Robert-Koch-Institute, Berlin

Highly pathogenic (dangerous) influenza strains elicit a strong immune response which can lead to uncontrolled inflammation in the lung and potentially fatal lung injury. A study published on May 8th in PLOS Pathogens demonstrates the importance of IL-27 for the control of immunopathology—damage to the lung tissue caused by the immune system—and the therapeutic potential of well-timed IL-27 application to treat life-threatening inflammation during lung infection.

Alf Hamann, from Deutsches Rheuma-Forschungszentrum and Charité Universitätsmedizin Berlin, Germany, and colleagues, did a comprehensive analysis of IL-27 function in mice infected with a highly pathogenic influenza strain. They found that IL-27 levels in infected lungs follow, with some delay, the level of : they peak as viral levels are starting to decline and come down when immunopathology has resolved. This is compatible with a role for IL-27 in dampening uncontrolled inflammation at later stages of the infection, while initially allowing for a rapid immune defense.

When the researchers examined mice with disrupted IL-27 function, they found that they were more likely than normal mice likely to die when infected with the virus, and that they died as a consequence of rampant . This was associated with a stronger and stronger immunopathology. Thus, IL-27 plays an important role in limiting destructive inflammation during the advanced stages of infection.

Having discovered the crucial role of IL-27 in regulating immunopathology, the researchers wondered whether this could be exploited for therapeutic purposes. To test the potential of IL-27 treatment, they administered recombinant IL-27 (rIL-27, that is, IL-27 produced by biotechnology) to normal mice at different times after .

Control of inflammation by local and systemic action of IL-27 in influenza. Credit: Alf Hamann et al.

When they matched the natural course of IL-27 (treatment starting at day 5 after virus infection), they found that fewer mice died, that they lost less weight, and recovered quicker than those without treatment. In contrast, mice treated with IL-27 early (starting at the day of virus infection) were doing poorly and did not recover from the infection. Although their lungs showed less extensive damage, they were not able to control overall virus levels. This shows the importance of timing, with IL-27 treatment being beneficial only during later stages of infection but harmful when given too early.

The scientists conclude that in "well-timed treatment with rIL-27 improved and accelerated recovery without affecting viral clearance" and continue "these data demonstrate that IL-27 has a unique role in controlling immunopathology without impacting on host defense, and might therefore represent a promising candidate for immunomodulatory therapy of viral pneumonia."

Explore further: Immunologists find a molecule that puts the brakes on inflammation

More information: Liu FDM, Kenngott EE, Schröter MF, Kühl A, Jennrich S, et al. (2014) Timed Action of IL-27 Protects from Immunopathology while Preserving Defense in Influenza. PLoS Pathog 10(5): e1004110. DOI: 10.1371/journal.ppat.1004110

Related Stories

Slowing down the immune system when in overdrive

February 10, 2014

Many people suffer from chronic inflammation because their immune systems overreact to 'self' tissue. Sydney scientists believe that a small molecule known as Interleukin 21 is a promising therapeutic target in such cases.

Recommended for you

We've all got a blind spot, but it can be shrunk

August 31, 2015

You've probably never noticed, but the human eye includes an unavoidable blind spot. That's because the optic nerve that sends visual signals to the brain must pass through the retina, which creates a hole in that light-sensitive ...

Biologists identify mechanisms of embryonic wound repair

August 31, 2015

It's like something out of a science-fiction movie - time-lapse photography showing how wounds in embryos of fruit flies heal themselves. The images are not only real; they shed light on ways to improve wound recovery in ...

New 'Tissue Velcro' could help repair damaged hearts

August 28, 2015

Engineers at the University of Toronto just made assembling functional heart tissue as easy as fastening your shoes. The team has created a biocompatible scaffold that allows sheets of beating heart cells to snap together ...

Fertilization discovery: Do sperm wield tiny harpoons?

August 26, 2015

Could the sperm harpoon the egg to facilitate fertilization? That's the intriguing possibility raised by the University of Virginia School of Medicine's discovery that a protein within the head of the sperm forms spiky filaments, ...

Research identifies protein that regulates body clock

August 26, 2015

New research into circadian rhythms by researchers at the University of Toronto Mississauga shows that the GRK2 protein plays a major role in regulating the body's internal clock and points the way to remedies for jet lag ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.