Markers of inflammation identify br cancer survivors with FATIGUE

[Lani]

Inflammation Markers Identify Fatigue In Breast Cancer Survivors

Main Category: Breast Cancer News
Article Date: 03 May 2006 - 7:00am (PDT)

Researchers at the University of California, Los Angeles have defined conditions associated with disabling fatigue that persists for years in almost a third of breast cancer survivors, according to a study in the May issue of Clinical Cancer Research.

The key to their fatigue stems from responses within their immune systems.

"These studies identify a biological basis for persistent fatigue in cancer survivors that is implemented by inflammation," said Michael Irwin, M.D., director and senior research scientist, Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience, and the UCLA Jonsson Cancer Center.

"We have detected a biological marker that is a composite of two immune response elements," he added. "This biomarker identifies - and can predict - which women have long term persistent fatigue.

"These findings point the way for development of novel treatment strategies that decrease this inflammatory response and thwart the fatigue that these patients endure."

One component of the marker, Dr. Irwin explained, is a measure of the amount of interleukin-6 receptor (IL-6R) free-floating in the blood of breast cancer survivors compared to the amount of that receptor remaining on the membranes of specific blood cells - where the receptor normally is found and functions within the immune response.

The IL-6R is usually embedded on the surface membrane of white blood cells, or monocytes. In some survivors, however, many of the IL-6R are shed from the monocytes and are soluble within the blood plasma. Those free-floating receptors can still bind to circulating cytokine IL-6, Dr. Irwin noted, and in that form have the potential to interact with cells that normally don't respond to cytokine/receptor activation - such as brain cells that may regulate fatigue sensation.

IL6 is a biological chemical that helps drive initial immune responses within people. "IL-6 contributes to an activation of monocytes in the blood, and enables antigen presenting cells to activate T cells as part of the cellular immune response," Dr. Irwin said.

The second component of the marker is an index measured by the level of T cells that are characterized by CD69, a cell membrane protein that indicates early activation of those T cells. Patients with a decreased number of CD69+ T cells along with the high ratio of serum IL 6R/monocyte-bound IL-6R were likely to experience persistent fatigue.

Battling breast cancer is a daunting challenge to women diagnosed with the disease, but with advanced screening and treatment strategies, patients with early stage breast cancer are surviving longer. Breast cancer survivors are the largest group of patients to overcome any type of cancer in the United States. While patients surviving other types of cancer also can experience the long-lasting fatigue syndrome, a greater proportion of breast cancer survivors endure the condition.

Cancer researchers had explored various possible reasons for the persistent fatigue in breast cancer survivors, Dr. Irwin said, such as different kinds of treatment, or biological events including anemia.

Dr. Irwin and his colleagues' research is the first to document an association between biological mechanisms involved with the immune response and persistent fatigue.

"It is such an important quality of life issue. Many patients are surviving from their cancer treatments, but they are surviving with substantial impairments in their ability to carry on their lives," Dr. Irwin said. "We've addressed the cancer in these survivors, and now we can also address the functional declines in the quality of life of these patients."

Dr. Irwin defined the fatigue biomarker in collaboration with Alicia Collado-Hidalgo, Julienne E. Bower, Patricia A. Ganz, and Steve W. Cole, with the David E. Geffen School of Medicine at UCLA.

[janet/FL]

Thanks Lani
I wonder how to learn more about this? What markers and is there any treatment?
janet

[StephN]

Hi -
I just sent this to my doc to see if there is any way to test for these markers mentioned in the article.

Thanks again Lani - may explain some things about my fatigue.

[Lani]

FOR SOME REASON THE SIGN FOR ALPHA COMES OUT AS A ? WHEN I POST IT:

ABSTRACT: Cancer Chemotherapy-Related Symptoms: Evidence to Suggest a Role for Proinflammatory Cytokines
[Oncology Nursing Forum; Subscribe]
Purpose/Objectives: To provide an overview of the evidence that supports a role for the proinflammatory cytokines interleukin-1? (IL-1?), tumor necrosis factor-? (TNF-?), and interleukin-6 (IL-6) in the etiology of cancer chemotherapy-related symptoms.

Data Sources: Electronic nursing, psychology, and medicine databases; online meeting abstracts; and personal experimental observations.

Data Synthesis: Substantial evidence implicates the proinflammatory cytokines IL-1?, TNF-?, and IL-6 in the etiology of chemotherapy-related anorexia, cachexia, anemia, pain, sleep disturbance, fatigue, and depression.

Conclusions: Further investigation into the role of these cytokines in the genesis of chemotherapy-related symptoms is warranted. The development of appropriate animal models likely will be key to understanding the relationship among cancer chemotherapy, proinflammatory cytokines, and symptoms.

Implications for Nursing: Nurses traditionally have been leaders in symptom management. The symptoms experienced by patients undergoing chemotherapy have a profound negative impact on quality of life and patients' ability to receive prescribed treatments. An understanding of potential mechanisms underlying the physiologic and behavioral consequences of chemotherapy administration will aid nurses in the development of interventions to effectively manage chemotherapy-related symptoms.

[R.B.]

Fascinating.

The omega six pathways that produces the cox 2s etc is recognised as being involved in the inflamatory process and diseases.

Several writers potulate theories of omega six being a percussor to low grade inflamatory disease intitially will lead to a growing cylce as the body is oversupplied in omega six, fuleing more inflamation using more availabe six etc.

PPARs intereact with IL6. Ppars interacts with various fats.

Thanks

RB

[Sue2001]

This is very interesting -- thanks for the post.

It's difficult to explain to others what this fatigue feels like. I've always wondered why it didn't go away after treatment stopped. Sometimes I've thought it's all in my mind.

Thanks, Sue

[R.B.]

You might like to read Smart Fats by Schmidt published by Frog Limited.

It is primarily about fats and brain health. It is well written punchy rings alarm bells (and for me filled in a lot of half formed ideas and questions on things like post natal depression).

It puts things in powerful and understandable ways.

It does not relate directly to BC but is none the less well worth a read particularly for Mums with children etc.

Oh almost forgot the point of the post - Fats can play a part in fatigue due to wider implications.

RB