Use of Growth Factors and Cytokines to Treat Injuries Resulting from a Radiation Public Health Emergency

Horta, Zulmarie Perez; Case, Cullen; DiCarlo, Andrea L.

doi:10.1667/rr15383.1

Cited by 6 publications

(3 citation statements)

References 30 publications

(24 reference statements)

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“…Maximal cytokine production occurs between 4 and 24 hours following exposure to short-term radiation [ 34 , 35 ]. The balance of proinflammatory and anti-inflammatory cytokines synthesized is critical in the determination of outcomes [ 36 ] with several factors altering the profiles of the cytokines produced including the specific animal species and tissue studied, the magnitude of the radiation received, and whether whole animals, portions of animals, or only cells were exposed [ 30 – 33 ]. Chronic exposure to very low-dose nonacute radiation can induce hormesis and alter the levels of several cytokines to improve tissue responses [ 30 , 35 ].…”

Section: Introductionmentioning

confidence: 99%

COVID-19: Proposing a Ketone-Based Metabolic Therapy as a Treatment to Blunt the Cytokine Storm

Bradshaw

Seeds²,

Miller

et al. 2020

Oxidative Medicine and Cellular Longevity

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Human SARS-CoV-2 infection is characterized by a high mortality rate due to some patients developing a large innate immune response associated with a cytokine storm and acute respiratory distress syndrome (ARDS). This is characterized at the molecular level by decreased energy metabolism, altered redox state, oxidative damage, and cell death. Therapies that increase levels of (R)-beta-hydroxybutyrate (R-BHB), such as the ketogenic diet or consuming exogenous ketones, should restore altered energy metabolism and redox state. R-BHB activates anti-inflammatory GPR109A signaling and inhibits the NLRP3 inflammasome and histone deacetylases, while a ketogenic diet has been shown to protect mice from influenza virus infection through a protective γδ T cell response and by increasing electron transport chain gene expression to restore energy metabolism. During a virus-induced cytokine storm, metabolic flexibility is compromised due to increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) that damage, downregulate, or inactivate many enzymes of central metabolism including the pyruvate dehydrogenase complex (PDC). This leads to an energy and redox crisis that decreases B and T cell proliferation and results in increased cytokine production and cell death. It is hypothesized that a moderately high-fat diet together with exogenous ketone supplementation at the first signs of respiratory distress will increase mitochondrial metabolism by bypassing the block at PDC. R-BHB-mediated restoration of nucleotide coenzyme ratios and redox state should decrease ROS and RNS to blunt the innate immune response and the associated cytokine storm, allowing the proliferation of cells responsible for adaptive immunity. Limitations of the proposed therapy include the following: it is unknown if human immune and lung cell functions are enhanced by ketosis, the risk of ketoacidosis must be assessed prior to initiating treatment, and permissive dietary fat and carbohydrate levels for exogenous ketones to boost immune function are not yet established. The third limitation could be addressed by studies with influenza-infected mice. A clinical study is warranted where COVID-19 patients consume a permissive diet combined with ketone ester to raise blood ketone levels to 1 to 2 mM with measured outcomes of symptom severity, length of infection, and case fatality rate.

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Section: Introductionmentioning

confidence: 99%

COVID-19: Proposing a Ketone-Based Metabolic Therapy as a Treatment to Blunt the Cytokine Storm

Bradshaw

Seeds²,

Miller

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…However, the use of stem cell transplantation is an expert decision and is very limited, only for patients who have no other organ systems that will not recover [51,52]. The primary objective of treatment is to support the autologous or stimulated recovery of the suppressed bone marrow and prevent or manage infectious/hemorrhagic complications of ARS [53]. In cases where the severity of radiation exposure has led to irreversible and life-limiting health consequences, some patients may qualify for palliative care, focusing on symptom management and improving their overall quality of life [50,51].…”

Section: Management At Decontamination Roommentioning

confidence: 99%

An Overview of Appropriate Medical Practice and Preparedness in Radiation Emergency Response

Al-Ibraheem,

Moghrabi,

Abdlkadir

et al. 2024

Cureus

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Radiation emergencies involving high doses of nuclear radiation pose significant risks from exposure to ionizing radiation in various scenarios. These situations include transportation accidents involving radioactive materials, occupational exposure, nuclear detonations, dirty bombs, and nuclear power plant accidents. In addition to the immediate risks of acute radiation syndrome (ARS) and related diseases, longterm exposure can increase the risk of other health issues such as cardiovascular disease and cancer. Vulnerable populations, including pregnant women and children, face particular concern due to potential impacts on their health and the health of unborn babies.The severity of ARS depends on several factors such as radiation dose, quality, dose rate, exposure uniformity, and individual biological responses. Bioindicators are biological responses or markers that help assess the severity and effects of radiation exposure on an individual. Bioindicators can include physical symptoms such as nausea, vomiting, and diarrhea, or laboratory tests such as changes in blood cell counts and gene expression that can help in assessing and treating exposed individuals. Additionally, early prodromal symptoms such as vomiting, diarrhea, and erythema can provide important clues for diagnosis and treatment. Developing a comprehensive plan for radiation emergencies is vital for safeguarding public health, infrastructure, and the environment.First responders play a critical role in establishing safety perimeters, triage, and coordination with various stakeholders. Education and training are essential for medical personnel and the public. This article provides general recommendations and identifies challenges to effective radiation emergency preparedness and response.

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“…Combinations of hematopoietic growth factors and cytokines (G-CSF, GM-CSF, EPO, SCF, and IL-3) have already been used in the treatment of radiological accident victims, but the relative efficacy of this combined treatment is difficult to evaluate due to differing radiation sources, exposure doses, and other circumstances [127].…”

Section: Anti-inflammatory Activitymentioning

confidence: 99%

Radioprotectors, Radiomitigators, and Radiosensitizers

Montoro,

Obrador,

Mistry

et al. 2023

Radiobiology Textbook

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This chapter gives an overview of molecules and mechanisms able to intervene with the biological effects of ionizing radiation (IR), either related to their clinical use in radiotherapy or in the field of radiation protection in case of an accidental exposure to radiation and/or nuclear emergencies. According to the National Cancer Institute, “radiomodifiers” can be classified into (a) radioprotectors (protect molecules and tissues from direct and indirect damage induced by IR) or (b) radiomitigators (reduce and help to repair damage), depending on whether they are administered pre- or post-IR exposure, respectively. Most of them are free radical scavengers and antioxidants (or enhancers of the antioxidant defenses), increase DNA repair mechanisms, have anti-inflammatory properties, and/or prevent cell death. On the other hand, (c) radiosensitizers directly or indirectly enhance DNA damage and ROS production, increasing IR toxicity on tumor cells, thus they are used to increase radiotherapy efficacy in cancer patients. The section “Radionuclides and methods to treat contaminated individuals” describes the medical consequences and treatment modalities of internal contamination by radionuclides. Overall, the chapter discusses the effects of most currently known radiomodifiers, their specific properties, and their mechanisms of action, by emphasizing results obtained in recent preclinical and clinical trials.

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Use of Growth Factors and Cytokines to Treat Injuries Resulting from a Radiation Public Health Emergency

Cited by 6 publications

References 30 publications

COVID-19: Proposing a Ketone-Based Metabolic Therapy as a Treatment to Blunt the Cytokine Storm

COVID-19: Proposing a Ketone-Based Metabolic Therapy as a Treatment to Blunt the Cytokine Storm

An Overview of Appropriate Medical Practice and Preparedness in Radiation Emergency Response

Radioprotectors, Radiomitigators, and Radiosensitizers

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