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1.  Cancer Control Related to Stimulation of Immunity by Low-Dose Radiation 
Dose-Response  2006;5(1):39-47.
Previous studies showed that low dose radiation (LDR) could stimulate the immune system in both animal and human populations. This paper reviews the present status of relevant research as support to the use of LDR in clinical practice for cancer prevention and treatment. It has been demonstrated that radiation-induced changes in immune activity follows an inverse J-shaped curve, i.e., low dose stimulation and high dose suppression. The stimulation of immunity by LDR concerns most anticancer parameters, including antibody formation, natural killer activity, secretion of interferon and other cytokines as well as other cellular changes. Animal studies have revealed that LDR retards tumor growth, decreases cancer metastasis, and inhibits carcinogenesis induced by high dose radiation. These effects of LDR on cancer control were found to be related to its stimulation on immunity. The experimental data may well explain the efficacy of the clinical trial of LDR in the treatment of cancer.
doi:10.2203/dose-response.06-108.Liu
PMCID: PMC2477702  PMID: 18648611
2.  Radiation-Induced Change in Lymphocyte Proliferation and its Neuroendocrine Regulation: Dose–Response Relationship and Pathophysiological Implications 
Cellular activities are regulated by intracellular signals initiated by stimulation from the external and internal environments. Different signal pathways are involved in the initiation of different cellular functions. In connection with cell proliferation in response to mitogenic stimulation, the dose–effect relationship of the magnitude of 3H-TdR incorporation into lymphocytes after exposure to different concentrations of concanavalin A (Con A) showed an inverted U-shaped curve in the concentration range 2–30 μg/ml. In previous studies it has been observed that the stimulatory effect of Con A (5 μg/ml) on lymphocyte proliferation was potentiated by whole-body irradiation (WBI) with low dose (0.075 Gy) and suppressed by WBI with high dose (2 Gy). When different concentrations of corticosterone, ranging from 10–12 to 10–7 M, were added to the Con A–stimulated lymphocytes, low-concentration stimulation and high-concentration suppression of lymphocyte proliferation were demonstrated. In the presence of 5 ×10 –12 M (subphysiological concentration) of corticosterone the proliferation of thymocytes and splenic T cells in response to Con A was further up-regulated after low-dose radiation. Low-dose radiation (0.075 Gy) caused lowering of serum ACTH and corticosterone concentration as well as down-regulated transcription of the hypothalamic proopiomelanocortin gene. The present paper intends to show that multiple neurohormonal factors, including the pineal gland and neurotransmitters, in addition to the hypothalamic–pituitary–adrenocortical axis, are involved in the stimulation of immune responses induced by low-dose ionizing radiation. The complex nature of the interrelationship between the intracellular signaling of lymphocytes and the neuroendocrine regulation after WBI is discussed.
doi:10.1080/15401420490507486
PMCID: PMC2657486  PMID: 19330146
lymphocyte proliferation; nonlinear dose-response curve; signal molecules; neuroendocrine regulation; pineal gland; catecholamines
3.  Nonlinear Dose-Response Relationship in the Immune System Following Exposure to Ionizing Radiation: Mechanisms and Implications 
The health effects of low-dose radiation (LDR) have been the concern of the academic spheres, regulatory bodies, governments, and the public. Among these effects, the most important is carcinogenesis. In view of the importance of immune surveillance in cancer control, the dose-response relationship of the changes in different cell types of the immune system after whole-body irradiation is analyzed on the basis of systemic data from the author’s laboratory in combination with recent reports in the literature. For T lymphocytes J- or inverted J-shaped curves are usually demonstrated after irradiation, while for macrophages dose-response curves of chiefly stimulation with irregular patterns are often observed. The intercellular reactions between the antigen presenting cell (APC) and T lymphocyte (TLC) in the immunologic synapse via expression of surface molecules and secretion of cytokines by the two cell types after different doses of radiation are illustrated. The different pathways of signal transduction thus facilitated in the T lymphocyte by different doses of radiation are analyzed to explain the mechanism of the phenomenon of low-dose stimulation and high-dose suppression of immunity. Experimental and clinical data are cited to show that LDR retards tumor growth, reduces metastasis, increases the efficacy of conventional radiotherapy and chemotherapy as well as alleviates the suppression of immunity due to tumor burden. The incidence of thymic lymphoma after high-dose radiation is lowered by preexposure to low-dose radiation, and its mechanism is supposed to be related to the stimulation of anticancer immunity induced by low-dose radiation. Recent reports on lowering of standardized cancer mortality rate and all cause death rate of cohorts occupationally exposed to low-dose radiation from the US, UK, and Canada are cited.
PMCID: PMC2651616  PMID: 19330113
dose-response curves; immune surveillance; molecular and cellular mechanisms; cancer risk
4.  Role of CD28/B7 costimulation and IL-12/IL-10 interaction in the radiation-induced immune changes 
BMC Immunology  2001;2:8.
Background
The present paper aims at studying the role of B7/CD28 interaction and related cytokine production in the immunological changes after exposure to different doses of ionizing radiation.
Results
The stimulatory effect of low dose radiation (LDR) on the proliferative response of lymphocytes to Con A was found to require the presence of APCs. The addition of APCs obtained from both low- and high-dose-irradiated mice to splenic lymphocytes separated from low-dose-irradiated mice caused stimulation of lymphocyte proliferation. B7-1/2 expression on APCs was up-regulated after both low and high doses of radiation. There was up-regulation of CD28 expression on splenic and thymic lymphocytes after LDR and its suppression after high dose radiation (HDR), and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) expression showed changes in the opposite direction. IL-12 secretion by macrophages was stimulated after both low and high doses of radiation, but IL-10 synthesis by splenocytes was suppressed by low dose radiation and up-regulated by high dose radiation.
Conclusion
The status of CD28/CTLA-4 expression on T lymphocytes in the presence of up-regulated B7 expression on APCs determined the outcome of the immune changes in response to radiation, i.e., up-regulation of CD28 after LDR resulted in immunoenhancement, and up-regulation of CTLA-4 associated with down-regulation of CD28 after HDR led to immunosuppression. Both low and high doses of radiation up-regulated B7-1/2 expression on APCs. After LDR, the stimulated proliferative effect of increased IL-12 secretion by APCs, reinforced by the suppressed secretion of IL-10, further strengthened the intracellular signaling induced by B7-CD28 interaction.
doi:10.1186/1471-2172-2-8
PMCID: PMC48143  PMID: 11532194

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