Sydney researchers explain how stress can make you sick

13 June 2007

Garvan Institute scientists have discovered how a hormone, known as neuropeptide Y (NPY), can prevent our immune system functioning properly, paving the way for two new major opportunities for therapeutic intervention.

"Most of us expect to come down with a cold or other illness when we are under pressure, but until now we have mostly had circumstantial evidence for a link between the brain and the immune system", says lead Garvan researcher Associate Professor Fabienne Mackay.

"During periods of stress, nerves release a lot of NPY and it gets into the bloodstream, where it inhibits the cells in the immune system that look out for and destroy pathogens (bacteria and viruses) in the body," explains Mackay.

This significant discovery came about through a collaboration between Mackay's immunology group and scientists in the Neurobiology program at the Garvan Institute of Medical Research, Sydney, Australia.

Associate Professor Herbert Herzog who heads the Neurobiology program says, "Elite athletes are particularly prone to illness, possibly because of the extreme physical and emotional stressors associated with competition. But our research is relevant to everyone because there is no escaping stress - be it in the workplace or at home. Employment surveys1 show many workers feel there is more job-related stress today than even a couple of years ago".

Absenteeism, around 30% of which can be attributed to own ill health or physical disability2, costs well over $10 billion Australian dollars a year3, so now more than ever employers should be thinking about how to reduce stress in the hope that their workforce will be healthier.

The Garvan Institute study centres on two key events that enable our bodies to recognise foreign substances and control invaders. When we encounter a pathogen (bacteria and viruses), the immune 'sentry' cells that are on guard duty retain and interrogate the suspects. Their activation is made possible by NPY. These cells then return to the lymph nodes, which are found all over the body, with information about the foreign invaders. The lymph nodes are where decisions about defense are made.

In the case of bacteria and viruses, TH1 cells are part of the attack team that is sent out on the 'search and destroy' mission. But when their job is done they need to be turned 'off' and the immune system reset. The same hormone, NPY, that activates the sentry cells now prompts the TH1 cells to slow down and die.

Mackay adds that: "Under normal conditions, circulating immune cells produce small amounts of NPY, which enables the immune cells on sentry duty and the TH1 immune cells to operate - it's a yin and yang kind of situation. But too much NPY means that the TH1 attack is prevented despite the foreign invaders being identified - and this is what happens during stress",

Understanding the connection between NPY and the immune system offers two new major opportunities for therapeutic intervention. The first is to design new drugs to stimulate immune system defences in people exposed to high levels of stress, such as in a bereavement situation, and in immuno-compromised individuals. The second is to exploit this Th1 inhibitory mechanism to prevent immune responses getting out of control as in various inflammatory and autoimmune diseases such as Crohn's disease, rheumatoid arthritis, multiple sclerosis, type I diabetes and lupus.



Associate Professor Fabienne Mackay is a Principal Research Fellow in the Arthritis and Inflammation Research Program at the Garvan Institute and a Conjoint Associate Professor, Faculty of Medicine, University of NSW and University of Sydney. She is also a Wellcome Trust Senior Research Fellow.

Associate Professor Herbert Herzog is a Principal Research Fellow and the Director of the Neurobiology Program at the Garvan Institute. He is also a National Health and Medical Senior Research Fellow; an Adjunct Associate Professor at the Faculty of Medicine, University of New South Wales; and an Associate Professor for Biochemistry, Department of Biochemistry, Free University of Berlin.

Wheway J, Mackay CR, Newton RA, Sainsbury A, Boey D, Herzog H, Mackay F. A fundamental bimodal role for neuropeptide Y1 receptor in the immune system. J Exp Med. 2005 Dec 5;202(11):1527-38.