New research shows that chronic stress
changes gene activity in immune cells before they reach the bloodstream. With
these changes, the cells are primed to fight an infection or trauma that
doesn’t actually exist, leading to an overabundance of the inflammation that is
linked to many health problems.
This is not just any stress, but repeated
stress that triggers the sympathetic nervous system, commonly known as the
fight-or-flight response and stimulates the production of new blood cells.
While this response is important for survival, prolonged activation over an
extended period of time can have negative effects on health.
A study in animals showed that this type of
chronic stress changes the activation, or expression, of genes in immune cells
before they are released from the bone marrow.
Genes that lead to inflammation
are expressed at higher-than-normal levels, while the activation of genes that
might suppress inflammation is diminished.
Chronically stressed people
Ohio State University scientists made this
discovery in a study of mice.
Their colleagues from other institutions, testing
blood samples from humans living in poor socio-economic conditions, found that
similarly primed immune cells were present in these chronically stressed people
professor of oral biology in the College of Dentistry and associate director of
Ohio State’s Institute for Behavioural Medicine Research and co-lead
author of the study, said: "The cells share many of the same
characteristics in terms of their response to stress.“There is a stress-induced alteration in the bone marrow
in both our mouse model and in chronically stressed humans that selects for a
cell that’s going to be pro-inflammatory.
“So what this suggests is that if you’re
working for a really bad boss over a long period of time, that experience may
play out at the level of gene expression in your immune system.”
Health problemsThe findings suggest that drugs acting on
the central nervous system to treat mood disorders might be supplemented with
medications targeting other parts of the body to protect health in the context
of chronic social stress.
Steven Cole, a professor of medicine and a
member of the Cousins Centre for psycho-neuro-immunology at the University of California, Los Angeles, is a co-corresponding author of the study.
The research was published in a recent
issue of the journal Proceedings of the National Academy of Sciences.
The mind-body connection is well
established and research has confirmed that stress is associated with health
problems. However, the inner workings of that association – exactly how stress can
harm health – are still under investigation.
Fight or flight
Sheridan and colleagues have been studying
the same model for a decade to reveal how chronic stress – and
specifically stress associated with social defeat – changes the brain and body
in ways that affect behaviour and health.
The mice are repeatedly subjected to stress
that might resemble a person’s response to persistent life stressors. In the model, male mice living together are given time to establish a hierarchy and then
an aggressive male is added to the group for two hours at a time. This elicits
a “fight or flight” response in the resident mice as they are repeatedly
defeated by the intruder.
“These mice are chronically in that state,
so our research question is, ‘What happens when you stimulate the sympathetic
nervous system over and over and over or continuously?’ We see harmful consequences to that,” Sheridan said.
what this suggests is that if you’re working for a really bad boss over a long
period of time, that experience may play out at the level of gene expression in
your immune system.”
Under normal conditions, the bone marrow in
animals and humans is making and releasing billions of red blood cells every
day, as well as a variety of white blood cells that constitute the immune
Sheridan and colleagues already knew from previous work that stress
skews this process so that the white blood cells produced in the bone marrow
are more inflammatory than normal upon their release – as if they are ready to
defend the body against an external threat.
A typical immune response to a pathogen or
other foreign body requires some inflammation, which is generated with the help
of immune cells. But when inflammation is excessive and has no protective or
healing role, the condition can lead to an increased risk for cardiovascular
diseases, diabetes and obesity, as well as other disorders.
In this work, the researchers compared
cells circulating in the blood of mice that had experienced repeated social
defeat to cells from control mice that were not stressed.
The stressed mice had
an average fourfold increase in the frequency of immune cells in their blood
and spleen compared to the normal mice.
Genome-wide analysis of these cells that
had travelled to the spleen in the stressed mice showed that almost 3 000 genes
were expressed at different levels – both higher and lower – compared to the
genes in the control mice. Many of the 1 142 up-regulated genes in the immune
cells of stressed mice gave the cells the power to become inflammatory rapidly