General effects of inflammation on the body
So within the body, inflammation has a number of different effects. It can induce redness around any point of infection or inflammation, and also at the same time a certain tenderness. So, whenever we get an infection or inflammation within the body, we notice that it becomes red and quite tender around that region. That can equally apply to things like muscles, if there's inflammation within a muscle it can become inflamed, it can become tender to the touch and then also painful to use. And one also tends to see a loss of function. So if there's inflammation within a particular organ in the body, it becomes more difficult to use that organ. So, for example, within muscles, When muscles, the muscle becomes weaker.
General effects of inflammation on the brain and relation to feelings of fatigue
So inflammation also has a number, quite a large number, of different effects on the brain. Perhaps one of the most obvious ones and ones that we've known about for many, many years, is that when we get an infection, our body temperature increases and that is an effect that's governed by an effect of inflammation on the brain. So the hypothalamus, a particular part of the brain that regulates body temperature senses inflammation, proteins induced by the immune system, and resets our body temperature to a slightly higher level.
Inflammation also has a number of other actions on the brain. For example, the reduction in appetite and the reduction in desire to drink are also effects that are controlled to some degree by the brain: so when we become infected and inflamed, and this inflammation reduces our desire to eat and to drink.
But inflammation also has a number of other very interesting effects on our behaviour. So, for example, when we become inflamed, we typically experience a light reduction in mood, perhaps even a degree of irritability but we also experience things like subjective feelings of fatigue, difficulty concentrating, difficulty focusing and also a slight reduction in our memory performance.
Other aspects inflammation can also impair are social behaviours, we tend to isolate ourselves more if we become infected and inflamed, and don't want to socialise or to perform, I guess, more novelty seeking type behaviours.
These symptoms as a cluster are known as sickness behaviours and we all experience them whenever we get any infection like the flu, for example.
Different responses to an inflammation in ME
So again I think this is a very interesting question and currently I think the answer to that is poorly understood and this is something that we are currently actively looking at.
So the question is whether somebody with ME responds differently to an inflammatory challenge to someone who doesn't have ME and I think there could be a few different answers to this and that's what we are currently looking at. But one could be that perhaps people with ME have a more aggressive inflammatory response to an inflammatory challenge in the blood or in the periphery or it could be that their response is exactly the same as somebody who doesn't have ME. And then the question would arise, well, are there differences within the way their brain processes that inflammatory challenge. So, for example, does their brain respond more aggressively or in a more, in a greater manner, to an inflammatory challenge than somebody who doesn't have ME?
So at the moment, I think that's a very good question, it's something we are looking at. There is no answer at the moment but hopefully there will be within the next year or two when we look specifically at this question.
Different effects of inflammation
So do all infections have the same effects on the body and on the brain? And again, this is an area of emerging research that, looking at our own research and other groups, there do seem to be some differences in the way that, for example, viral infections or bacterial infections or models of these different types of infection affect the brain. It's quite unclear why this is the case, but it seems that some of the proteins that are activated by different types of infection may have slightly different effects on the brain. So this is an area that we're currently researching, really trying to address are particular parts more sensitive to some types of infection or inflammation compared to others.
Interferon
So what is interferon? Interferon is a cytokine, it's a protein that our bodies naturally produce whenever we become infected and in particular when we become infected by viruses.
There are a number of different types of interferon, but one that is particularly interesting is interferon alpha. And this is also used therapeutically to help treat patients with chronic hepatitis C. And if it's used in combination with other drugs can actually cure quite a high percentage of people with chronic hepatitis C.
However what it also does is that it induces quite severe cognitive and mood changes when it's given to patients. And perhaps one in four to one in three patients who's given interferon alpha chronically develops depression. So it's very clear that by activating the immune system with interferon, we can induce depression, severe fatigue, and a number of other cognitive difficulties in previously relatively healthy individuals.
And just on this point, another interesting phenomenon is that these patients who are treated with chronic interferon, even though their hepatitis C may be cured, there's a percentage of them who go on to experience chronic fatigue chronic cognitive impairment even after the treatment is over.
So again this is potentially a very good model to look at the long term effects of activating the immune system. Why is it that symptoms of fatigue and cognitive impairment persist even after the immune activation ceases?