Donders Wonders

The reason why the flu makes you feel miserable

This post is also available in Dutch.

Illness makes you feel miserable and lie in bed all day. What is the reason for this and what happens in your brain when you are sick?

Illness makes us feel miserable.

Picture from Pexels (License: CC0 1.0)

We probably all know this situation: We get the flu, feel miserable, and let our mother come over to cook us dinner. Going to the supermarket yourself seems too effortful. When a virus enters the body, it activates the body’s defense system by inducing the release of small proteins called cytokines. These cytokines are important for regulating our body temperature, and they also send messages to our brain to alter our mood and behaviour during illness. The so-called “sickness syndrome” includes fatigue, depression, and changes in our motivation. In other words, it is

 The flu affects your motivation
Research has shown that cytokines can reach the central nervous system where they affect the neurochemical dopamine. Dopamine is a neurotransmitter well-known for its role in the motivation to engage in activities. It can make you cook all day, because this leads to enjoying a tasty dinner with your best friends. However, this motivation changes when you are ill.

In a recent study at the radboudUMC in Nijmegen, researchers tested motivational behaviour during an experimental procedure that mimics illness. This is done by the administration of Lipopolysaccharide, a component of outer membrane of gram-negative bacteria, which activates the innate imuune system. When infused in the body, it is recognized as a bacterial infection, and the body responds with the release of pro-inflammatory cytokines. This induces a few hours of nausea, shivering, fatigue and feeling miserable. When the body discovers it was a false alarm, it recovers back to normal.

During this short period of illness, the young men participating in the experiment were asked whether they wanted to invest a certain level of physical effort (squeezing a hand grip) to earn a certain amount of money in a series of offers. The ill men still liked high rewards, but they more often declined the offer when effort levels were high. The ability to provide the physical effort was still intact. This provided evidence that acute illness indeed affects the motivation to engage in effortful activities. In other words, you still prefer the food your partner/mother cooks, but if you’d have to cook it yourself, you might choose for an easier, less tasty option.

From adaptive to maladaptive behaviours
Altered motivation and fatigue earning about how pro-inflammatory cytokines affect our brain and behavior can therefore provide important insights on why fatigue and altered motivation persist after severe illness. This will hopefully lead to new ways of treating and preventing long-lasting fatigue.


This blog was written by guest blogger Marieke van der Schaaf. Marieke is a Post Doc researcher studying the neurobiological mechanisms of fatigue at the Donders Institute.

Edited by Francie Manhardt.

Further reading

Effort but not Reward Sensitivity is Altered by Acute Sickness Induced by Experimental Endotoxemia in Humans. Draper A, Koch RM, van der Meer JW, Apps M, Pickkers P, Husain M, van der Schaaf ME. Neuropsychopharmacology. 2017


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