Inflammation is a normal response to protect the body from harmful
stimuli, but if the inflammation is chronic, it is destructive and can
In a paper published in Biology Open
, researchers reported that zebrafish embryos that are chronically exposed to
the stress hormone cortisol for just the first few days of life develop
into adults with abnormal immune systems and signs of chronic
‘The effects of environmental conditions before and immediately after birth on adult health has been highlighted in this study. Early-life stress increases vulnerability to inflammation and immune dysfunction.’
Scientists have long known that chronic exposure to psychosocial
stress early in life can lead to an increased vulnerability later in
life to diseases linked to immune dysfunction and chronic inflammation,
including arthritis, asthma, cancer, diabetes, heart disease and even
mental illness. But the molecular mechanisms underlying the negative
effects of early exposure to stress are unknown.
Using the common aquarium fish, the zebrafish, as a model, developmental biologist James A. Coffman, of the MDI Biological Laboratory in Bar Harbor, Maine, and his team are beginning to elucidate these mechanisms.
Coffman explained, "Chronic psychosocial stress
increases the level of cortisol circulating in the body, and if this
happens early in life it can influence how the body develops. So our
research helps explain why young children who experience chronic
psychosocial stress, due for example to low socioeconomic status,
economic insecurity, abuse or neglect, are more vulnerable as adults to
health problems associated with inflammation and immune dysfunction."
The paper was co-authored by Elli I. Hartig, Shusen Zhu and Benjamin L. King, all of the MDI Biological Laboratory.
"These findings contribute to the growing body of knowledge about
the effects of environmental conditions before and immediately after
birth on adult health," said Kevin Strange,
president of the MDI Biological Laboratory. "Research in this emerging
field suggests that interventions to mitigate the effects of early-life
stress could one day lead to significant improvements in public health."
Coffman's interest in studying the molecular mechanisms underlying
the contribution of stress to aging was piqued by the observation that
the rate of aging is often accelerated in chronically stressed
individuals, he said.
In the study, Coffman's team treated zebrafish embryos with
cortisol, a hormone that is naturally produced by the body in response
to stress. They then let those fish grow to adulthood and examined their
ability to regenerate their tailfins following surgical removal.
Specifically, the team looked at gene expression during the early stages
of regeneration, when the innate immune system mounts an inflammatory
response to the injury that is then rapidly resolved.
Zebrafish were used because of their extraordinary regenerative
ability, and because both the cortisol-mediated stress response and
innate immune system are essentially the same in zebrafish as they are
In adult zebrafish derived from cortisol-treated embryos,
inflammatory genes displayed a strikingly abnormal response to the
tailfin injury, which correlated with impaired regeneration. It was also
found that the innate immune system failed to mount a normal response
to molecular signals that are presented by infectious bacteria.
Coffman believes the aberrant immune gene regulation that his team
observed in the adults derived from cortisol-treated embryos is due to
glucocorticoid-induced developmental programming. In other words,
early-life exposure to chronically elevated cortisol results in lasting
developmental changes that affect processes critical for immune system
function and regulation throughout adult life.
The next step is to identify the specific ways that development of
the immune system is altered by chronically elevated cortisol, and
dissect the molecular mechanisms underlying those alterations, Coffman