In
a very promising preliminary study, Miller and colleagues found that
the pattern of gene expression differed between caregivers of family
members with cancer relative to a matched group of individuals who did
not have this type of life stress. They found that among the
caregivers, even though they had normal cortisol levels in their blood,
the pattern of gene expression in the monocytes, a type of white blood
cell involved in the body's immune response, was altered so that they
were relatively less responsive to the anti-inflammatory actions of
cortisol, but relatively more responsive to pro-inflammatory actions of
a transcription factor called nuclear factor-kappa B, or NF-κB. Gregory
Miller, Ph.D., corresponding author, explains more simply that,
although "caregivers have similar cortisol levels as controls, their
cells seem to be 'hearing' less of this signal. In other words,
something goes awry in caregivers' white blood cells so they are not
able to 'receive' the signal from cortisol that tells them to shut down
inflammation."
Thus, the current findings might help to explain
why the caregivers would seem to be in a chronic pro-inflammatory
state, a condition of immunologic activation. This activated state
could contribute to the risk for a number of medical illnesses, such as
depression, heart disease, and diabetes. Dr. Miller remarks that part
of the importance of these findings is "because people have
traditionally thought that higher cortisol is the reason that stress
contributes to disease, but this work shows that, at least in
caregivers, it's actually the opposite - there's too little cortisol
signal being heard by the cells, rather than too much."
However, many important related questions still remain unanswered, as noted by John H. Krystal, M.D., Editor of Biological Psychiatry
and affiliated with both Yale University School of Medicine and the VA
Connecticut Healthcare System. He comments that in addition to not
knowing how stress produces these altered patterns of gene expression
in the immune system, "we don't know how to account for the resilience
of some stressed people exposed to severe sustained stress or the
vulnerability of some people to relatively mild stress." He adds that
"the better that we understand the underlying molecular mechanisms that
link stress to illness, the more likely we are to make progress in
answering these important questions," and this article is certainly a
vital step in that direction.
Source: EurekAlert (Press Release)
