Stroke and “fight-or-flight” response weakens the immune system

A new study has found that people who have had a stroke have fewer of a specific type of immune cell called B cells, which normally produce antibodies to fight off infections. Surprisingly, the same compromising immune changes were seen when healthy B cells were exposed to noradrenaline - a chemical released by the body after stroke, but also during stress, illness, or intense physical activity.

People who have had a stroke are more likely to develop infections such as pneumonia. These infections can impair recovery leading to more disability and affect other brain functions like memory, thinking and mood. Understanding why the immune system becomes weaker after stroke could help doctors prevent these infections and improve patient outcomes.

Earlier studies by Dr Laura McCulloch and Dr Barry McColl found that in animal models, stroke activates the system behind the fight-or-flight response, which includes the release of chemical noradrenaline.

This activation quickly impairs a group of immune cells called B cells, reducing their ability to produce protective antibodies, and was associated with vulnerability to infection. Until now, it was unclear whether the same thing happens in stroke patients.

In this study, researchers analysed blood samples from patients 24 - 48 hours after an ischaemic stroke, and compared them with samples from individuals who had not had a stroke.

They found that stroke patients had fewer B cells and that these remaining cells were also less effective at producing antibodies and special signalling proteins called cytokines, both of which are essential for fighting infections.

These findings confirm that stroke leads to the loss of important immune cells in patients and reduces the body’s ability to make protective antibodies. This highlights these pathways as important targets to help reduce infection after stroke.

The team also tested B cells from healthy volunteers. When these cells were exposed to noradrenaline in a lab, they showed the same responses as seen in stroke patients: increased cell death and reduced antibody production.

This suggests that activation of the fight-or-flight response itself, not just stroke, can impair immune function. Stress, illness, or extreme physical exertion may all influence how well B cells work.

Comparison of immune cells after stroke vs no stroke — Reduced numbers of immune cells (B cells) were found in the blood of patients 24–48 hours after an ischaemic stroke. When B cells remaining after stroke were stimulated with bacterial proteins (mimicking an infection), they were less able to produce protective antibodies and signalling proteins called cytokines than B cells not exposed to stroke.

The researchers are now studying how these immune changes after stroke may affect long-term recovery, including thinking and memory, as well as further damage to the brain’s blood vessels.

They are also exploring new treatments aimed at protecting or restoring B cell function after stroke, with the goal of reducing infections and improving recovery.

This research was a collaboration between the McCulloch lab and scientists from the UK Dementia Research Institute and Institute for Neuroscience and Cardiovascular Research in Edinburgh and the University of Manchester.

This work was funded by the Medical Research Council, NIHR, Wellcome Trust, The Royal Society, The Kennedy Trust for Rheumatology Research, Leducq Foundation Transatlantic Network of Excellence, Stroke-IMPaCT and UK Dementia Research Institute.

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