Cytokines, the radiation response and radiation fatigue



Cytokines are signalling molecules that facilitate cellular communication. There are many, many cytokines that impact on most cell types, but are of particular importance in immune reactions.
Cytokines in Radiation

Cytokines are released by many cells following radiation exposure, including endothelial cells, fibroblasts, immune cells and parenchymal cells. The interplay of these cytokines is thought to be responsible for the pathogenesis of many of the effects seen following radiation exposure. The other major effect of radiation is cell death, discussed elsewhere.
Radiation released cytokines fall into several categories:

Cytokines that attract immune cells: These chemokines cause immune cells to enter the tissue through several methods, including attractiong of the cells and increasing the gaps between endothelial cells. Examples include interleukin 1α and interleukin 6. Inflammatory cells cause numerous other changes to occur, such as cell death, promotion of fibrosis and swelling of the tissue. These cytokines are involved in both early and late reactions – for example, the erythema seen after skin treatment is due to inflammatory cytokines.
Cytokines that cause fibroblast differentiation and collagen production (TGFβ, PDGF): These cytokines cause fibroblasts to differentiate into fibrocytes, which actively produce collagen proteins. This leads to scarring of the tissue and is usually observed as a late effect. The cytokines which initiate this process are often released at the time of radiation.
Cytokines which cause cell death. The archetypal cytokine is Tumour Necrosis Factor α, although other death inducing proteins exist. These cytokines bind to cellular death receptors and promote apoptosis by releasing caspase 8. Cell death leads to activation of other cytokines and attracts immune cells.

Example: Cytokine Release Following Lung Radiation

Reference: Rubin et al (1995) A perpetual cascade of cytokines postirradiation leads to pulmonary fibrosis, here.

Elevated expression of cytokines has been shown to occur within days of radiation exposure. Important suspects in the development of fibrosis of the lung are:

Interleukin 1α (IL1α): This pro-inflammatory cytokine stimulates fibroblast differentiation into fibrocytes, increases collagen production, attracts immune cells (neutrophils, macrophages) and stimulates the haematopoietic system. It is released in two peaks following radiation exposure of lung tissue. The first peak occurs in the weeks following exposure, followed by reduced production between 8 – 16 weeks. IL1α production increases after several months, correlating with pathological signs of lung fibrosis.
Transforming Growth Factor β (TGFβ), Platelet Derived Growth Factor (PDGF): These two cytokines are potent stimulators of fibrosis. Both show increased expression shortly after radiation exposure, increasing the production of collagen from fibroblasts.”
end quote.

The role of the cytokine response to internal emtters is absent in the public narrative of nuclear authorities. The only documentation is found in relation to treatment dose radio therapy. There is no reason, given the findings of Pecher and Aebersold in by 1941, to suggest that internalised highly active radio emitters do initiate a cytokine response. It may be assumed that military authorites are familiar with this effect in the context of the nuclear battlefield as a syndrome apart from Acute Radiation Injury. That is, the fatique syndrome exists on its own and not only as part of the Acute Radiation Syndrome constellation of symptoms. It is in fact the military record of effects which most closely apply to nuclear victims, as, like nuclear victims, soldiers enter the nuclear battlefield in a fit state. Where the syndrome is exhibited by civlians after civil nuclear power plant disasters, the nuclear authorities dismiss and ignore the cytokine fatigue and inflamatory response. Preferring a model based upon an assumption of mental illness. (eg Japan modern day.)


Biol Res Nurs. 2004 Jan;5(3):203-10.
Levels of fatigue compared to levels of cytokines and hemoglobin during pelvic radiotherapy: a pilot study.
Ahlberg K, Ekman T, Gaston-Johansson F.

Sahlgrenska Academy, Göteborg University, Faculty of Health Caring Sciences, Institute of Nursing, Department of Oncology, Gothenburg, Sweden.

Cancer-related fatigue (CRF) is a prevalent and distressing symptom experienced by patients during cancer therapy. One proposed mechanism for the development of fatigue is the increased secretion of proinflammatory cytokines and/or the development of anemia. The major purpose of this pilot study was to investigate the levels of fatigue and cytokines during radiation therapy and determine whether there was a correlation between the two. A secondary purpose was to explore the relationships among hemoglobin values, cytokines, and fatigue. Participants included 15 women diagnosed with uterine cancer, who received curative external radiation therapy. Fatigue was assessed by a self-report instrument (Multidimensional Fatigue Inventory [MFI-20]) and hemoglobin and cytokines (Il-1, Il-6, and TNF-alpha) were measured before, during, and after radiotherapy. The degree of fatigue increased during radiotherapy without a significant change in IL-1, IL-6, or TNF-alpha levels. There was no significant correlation between changes in general fatigue and the changes in IL-1 and TNF-alpha. There was a significant negative correlation between the change in IL-6 and general fatigue. The hemoglobin levels did decrease significantly during radiotherapy, but there was no significant correlation between general fatigue and hemoglobin after 3 weeks of therapy or after the completion of therapy. In conclusion, pelvic radiotherapy in women with uterine cancer is associated with increased fatigue. There were no significant relationships between anemia or cytokine levels and fatigue. The pathogenesis of fatigue during radiation therapy remains to be elucidated.

[PubMed – indexed for MEDLINE]


2009;15:5534-5540. Published OnlineFirst August 25, 2009.
Clin Cancer Res

Julienne E. Bower, Patricia A. Ganz, May Lin Tao, et al.

Therapy for Breast and Prostate Cancer
Inflammatory Biomarkers and Fatigue during Radiation
been identified. Studies linking inflammatory processes to fatigue in cancer survivors led
us to test the hypothesis that activation of the proinflammatory cytokine network is asso-
ciated withfatigue symptoms during radiation therapy for breast and prostate cancer.
Experimental Design:
Individuals with early-stage breast (n = 28) and prostate cancer(n = 20) completed questionnaires and provided blood samples for determination ofserum levels of interleukin 1
β (IL-1β) and IL-6 at assessments conducted before, during,
and after a course of radiation therapy. Serum markers of proinflammatory cytokine
activity, including IL-1 receptor antagonist and C-reactive protein, were examined in
a subset of participants. Random coefficient models were used to evaluate the associ-
ation between changes in cytokine levels and fatigue.
As expected, there was a significant increase in fatigue during radiation treat-
tor antagonist were positively associated withincreases in fatigue symptoms (Ps < 0.05),
although serum levels of IL-1βand IL-6 were not associated withfatigue. These effects
remained significant (Ps < 0.05) in analyses controlling for potential biobehavioral con-
founding factors, including age, body mass index, hormone therapy, depression, and
sleep disturbance.
Results suggest that activation of the proinflammatory cytokine network
and associated increases in downstream biomarkers of proinflammatory cytokine activ-
ity are associated with fatigue during radiation
therapy for breast and prostate cancer.
(Clin Cancer Res 2009;15(17):5534–40) end quote, again, the most likely source of a similar study involving internally contaminated individuals who are healthy is in the miltary record, open or secret. The first act of the Manhattan Project in relation to the then rapid discovery of the fission products list was to contract Hamilton to inject the substance into animals. Fatigue in animals may be difficult to discerne. Hamilton used rodents and gold fish, others used beagles. The nuclear veterans and A bomb survivors were the human cohorts. Other than this people suffering serious disease
were the medical cohort.


Post-radiation syndrome as a NO/ONOO–cycle, chronic fatigue syndrome-like disease
Martin L. Pall
School of Molecular Biosciences, Washington State University, Pullman, WA 99164-4234, USA
Received 9 May 2008; accepted 12 May 2008
Post-radiation syndrome is proposed to be chronic fatigue syndrome (CFS) or a chronic fatigue syndrome-
like illness, initiated by exposure to ionizing radiation. This view is supported by the nitric oxide/peroxynitrite (NO/
ONOO–) cycle mechanism, the putative etiologic mechanism for CFS and related illnesses. Ionizing radiation may initiate illness by increasing nitric oxide levels via increased activity of the transcription factor NF-JB and consequent increased synthesis of the inducible nitric oxide synthase. Two types of components of the nitric oxide/peroxynitrite
cycle have been studied in post-radiation syndrome patients and shown to be elevated. The symptoms and signs of post-radiation syndrome and its chronicity are similar or identical to those of chronic fatigue syndrome and can be explained as being a consequence of nitric oxide/peroxynitrite cycle etiology. While the data available to test this view
are limited, it provides for the first time a comprehensive explanation for post-radiation syndrome. c 2008 Elsevier Ltd. All rights reserved

for study purposes : ” The complex chronic symptoms have
typically been found in persons both shortly after
exposure and continuing for years after such expo-
sure. Pastel[7] described the symptoms as includ-
ing ‘‘fatigue, sleep and mood disturbances,
impaired memory and concentration and muscle
and/or joint pain’’.
end quote.

There is little doubt in my mind that the condition as described is a strong warning to authorities that the confinement of symptomology due to acute radiation syndrome (radiation sickness) only is insufficient. Confining radiation fatique only to radiation administrated in medical treatments is like wise inadequate. For it is plain that right now many thousands of people in the former Soviet Republics suffer the condition.
The indications are that people in Japan are suffering the same syndrome as a result of the nuclear failure there.

Given the readiness in which the medical profession accepts the cytokine mediated radiation fatigue response as being a biochemical fact, it appears extremely cruel of world nuclear authorities, including its associated medicos (if you can call them that) to quickly pull out their copies of DSM IV and ascribe a mental condition to civilian victims of nuclear disaster, whereas in hospitals around the world treating doctors are thoroughly familar with this aspect of the radiation response.

It is in the systematic response to local radiological insult that the whole body participates in the consquence of localised internal emitters. Perhpas. The effect seems to be an inflamatory response and an immune suppression.

Nuclear veterans the world over may relate to the narrative above.

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