Immune systems and ageing

“Elderly people succumb to viruses 'because their immune systems work too hard',” The Daily Telegraph has reported. The newspaper says that new research into the immune system could also affect the way flu vaccination is planned.

This animal study tested immune responses and liver damage caused by a common virus, the herpes virus, in mice of different ages. When the researchers blocked part of the action of the immune system in older mice, they found that the mice survived with the virus for longer. This suggests that their immune systems where previously causing liver damage. However, whether the results of this animal study can be applied to humans is debateable and will need further careful research.

The Daily Telegraph reports one researcher’s suggestion that blocking some actions of the immune system may be better than immunisation for preventing human susceptibility to viral infections. The newspaper’s implication that this study might influence seasonal and swine flu vaccinations is not justified by this early research in mice.

Where did the story come from?

This research was carried out by Dr Heather W Stout-Delgado from the Department of Internal Medicine at the Yale University School of Medicine and other colleagues in the US. The work was supported by grants from the US National Institutes of Health and was published in the peer-reviewed science journal Cell Host & Microbe.

The Daily Telegraph’s coverage of this research was reasonable, but could imply that this study had more relevance to humans than is warranted.

What kind of research was this?

This animal study compared the immune system responses to a viral infection in aged mice and young mice. The study was well conducted and used a sound design to answer the researchers’ questions. They were specifically interested in understanding how ageing modifies the immune system’s inflammatory response to viral infection.

Early research such as this can suggest areas for future study in humans. Positive media coverage of early research could positively affect the funding of future research programmes.

What did the research involve?

The researchers explain that, as an individual ages, infection and cancer become more common, suggesting there is an impairment of immunity. The exact mechanism underlying this is unclear, but one theory is that ageing leads to reduced ability to overcome viral infections.

Substances called inflammatory mediators, or cytokines, are released by specific white blood cells of the immune system. These mediators are used by the body to carry signals between cells. One group of these mediators is called the interleukin 17 (IL17) family, and these are collectively responsible for many early inflammatory and allergic responses. Some members of the IL17 family trigger the production of further chemical messengers. It was this complex cascade of immune pathways in mice that the researchers were interested in investigating further. They focussed on one particular mediator called IL-17A.

The researchers used a herpes virus (HSV-2) to infect groups of young mice (2-4 months old), middle-aged mice (8-10 months) and aged mice (18-20 months). They then examined their blood for inflammatory substances, timed how long it took the mice to die and examined the livers of the mice after death.

They then tried blocking the action of IL-17A by introducing an anti-IL-17A antibody to further sets of mice, either before or after they were infected with the virus. The researchers measured the inflammatory responses in the three age groups of mice.

The results of this study have been well reported and analysed. The detailed description of the methods will allow other groups of scientists to perform similar tests to see if the results can be repeated and to explore related biological pathways.

What were the basic results?

The researchers observed a large difference in outcomes, which depended on the age of the mice. For example, almost none of the 16 young mice succumbed to the effects of HSV infection, even after 50 days. All 20 of the aged mice died within about eight days of being infected. After infection, levels of IL-17A rose dramatically in the aged mice compared to the young mice. Liver damage was responsible for the deaths of the mice.

When the researchers gave the mice the anti-IL-17A antibody, this protected them from the harmful effects of the virus. Even the six aged mice tested now survived for about as long as the younger mice that did not have the antibody’s protection.

How did the researchers interpret the results?

The researchers say that aged mice had defective immune responses, but instead of trying to boost their immune response, they tried to "inhibit certain inflammatory pathways to prevent susceptibility to viral infections”.

Their research also showed that the process of liver damage was dependent on the presence of cytokine IL-17A. They say that the findings show that unusual IL-17A responses to viral infection contribute to the death of the mice through a process that is dependent on the white cells (neutrophils).

In their paper, the researchers cautiously put forward the theory that, if the cells that produce IL-17 are increased in aged humans with viral infections, then age-dependent increases in IL-17 responses may have a role in human viral infections. They say this could explain why older people are more susceptible to infection from the seasonal flu virus.

In their press release, the researchers conclude more strongly that, "Our study could also explain why other susceptible populations succumb to viruses, such as the H1N1 pandemic virus, since it is possible that heightened immune responses – rather than defective immunity – attack the body and lead to disease in these individuals."

Conclusion

This well-conducted scientific study looked at complex immune pathways in mice and appears to have been over-interpreted in the study’s press release and lay media reports, which suggest that these findings have important implications for seasonal flu and H1N1 vaccination.

It is important that scientists study the complex mechanisms in animal and human immunity, and this early research warrants further exploration. However, given the experimental nature of this animal study, it is premature to conclude that this study is relevant to flu vaccination programmes.