Autonomic Neuroscience Group

We analyse the neural pathways of the inflammatory reflex. This is an unconscious reflex that regulates systemic inflammation in a negative feedback fashion. Inflammation is the first stage of the body’s response to injury or microbial invasion. It’s both good and bad; it’s necessary to mobilise immune defences but, if too intense, it can damage host tissues and endanger recovery.

The brain stem has evolved a mechanism that automatically helps to lessen the inflammatory response to an immune challenge and keep it within controllable limits. This mechanism dampens down the levels of pro-inflammatory cytokine hormones such as tumour necrosis factor (TNF), interleukin 6 and interferon-gamma, but at the same time, it enhances levels of the anti-inflammatory cytokine interleukin 10. We discovered that the output pathway from the brain to body runs in the splanchnic sympathetic nerves. If we cut these nerves to disable the reflex, the inflammatory response to the immune challenge is much stronger. This dampening effect of the inflammatory reflex can be seen to operate within minutes, but its consequences persist for a day or more.

Through our research, we are trying to define the central neurons that mediate the inflammatory reflex. So far, we have found that it is mediated from within the brain stem but does not require the hypothalamus.

A second line of study is identifying the neurochemical ‘signature’ of sympathetic ‘immuno-efferent’ neurons, using single-cell RNA analysis.

A third area of study is to try to understand the significance of this reflex for human health. We’ve already found that it plays an important role in the body’s ability to clear a systemic bacterial infection (sepsis). We are also investigating how the reflex affects antibody and cellular immune responses over the longer term (adaptive immunity).