Chronic stress alters our genetic immune response (8/28/2008)

Most people would agree that stress increases your risk for illness and this is particularly true for severe long-term stresses, such as caring for a family member with a chronic medical illness. However, we still have a relatively limited understanding of exactly how stress contributes to the risk for illness. In the August 15th issue of Biological Psychiatry, researchers shed new light on one link between stress and illness by describing a mechanism through which stress alters immune function.

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-?B. 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 th

The article is "A Functional Genomic Fingerprint of Chronic Stress in Humans: Blunted Glucocorticoid and Increased NF-?B Signaling" by Gregory E. Miller, Edith Chen, Jasmen Sze, Teresa Marin, Jesusa M.G. Arevalo, Richard Doll, Roy Ma, and Steve W. Cole. Drs. Miller, Chen, Sze, and Marin are affiliated with the Department of Psychology, University of British Columbia, Vancouver, Canada. Drs. Doll and Ma are with the British Columbia Cancer Agency, Vancouver Centre, Vancouver, Canada. Drs. Arevalo and Cole are from the Department of Medicine, Division of Hematology-Oncology, University of California Los Angeles (UCLA) School of Medicine, Los Angeles, California. Dr. Cole is also affiliated with the UCLA AIDS Institute, Molecular Biology Institute and Jonsson Comprehensive Cancer Center, and Norman Cousins Center at UCLA, Los Angeles, California. The article appears in Biological Psychiatry, Volume 64, Issue 4 (August 15, 2008), published by Elsevier.

Note: This story has been adapted from a news release issued by Elsevier

Post Comments: