One thing you have probably noticed when you have an
infection is a profound loss of appetite? In healthy adults, this could be seen
as something of a blessing, it can have much more serious consequences,
particularly at the extremes of age. In the elderly, the after effects of
respiratory infections can accelerate frailty and the loss of independence. In
the very young, not feeding can lead to dehydration and possibly contributes to
more severe disease.
In previous
studies, we observed that the loss of appetite was associated with the
immune response to infection. We were interested as to what might drive the loss
of appetite – with a view that understanding how it occurs might lead to
approaches to reverse it. In particular we wanted to understand one component
of the immune response – the cells that are recruited to the lungs to fight off
infections and the way that they communicate with other cells.
In our recently
published study we looked at one of the signals produced by immune cells, a
molecule called Interleukin 1 alpha (IL-1α for short). Cells release IL-1α to
warn the rest of the body that an infection is happening and as a way of
recruiting reinforcements to help in the fight. We saw that the peak of IL-1α
release into the lungs just precedes the weight loss, and therefore suspected
it played a role. To test our hypothesis (IL-1α causes weight loss during
infection) we took two approaches. Firstly, we blocked it during the course of
infection; when blocked there was no weight loss. Secondly, we added IL-1α by itself;
when we did this, we observed weight loss. Put together, these observations
strongly suggest that IL-1α released by immune cells reduces the appetite, and
leads to weight loss.
We then looked deeper into how this might happen. And we
found a really striking result – IL-1α levels increase in the brain during
infection. We think this is linked to an increase in permeability between the
brain and the rest of the body, which allows molecules to enter the brain which
would otherwise normally stay outside. The IL-1α in the brain then triggers a
cascade of hormones, in particular one called leptin, which is linked to feelings
of satiety (if leptin goes up, you feel full and stop eating). Famously mice
lacking the leptin gene are enormously fat because they never stop eating.
One other curiosity in our results was that when the mice
stop eating, the bacteria in their guts change. These changes increase certain
families of bacteria – some of which are linked to recovery from infection.
This suggests the intriguing possibility that there is a protective value in
not eating when you have a cold, because it increases protective bacteria – we have
yet to explore this fully.
Overall, we have dissected a pathway that links the immune
response to infection to a loss of appetite and discovered a key appetite
regulatory role for an immune molecule IL-1α. The next step is to explore how
this can be approached therapeutically.
