Immune Dysfunction from Radiation Exposure.

The hematopoietic system is highly sensitive to ionizing radiation. Damage to the immune system may result in opportunistic infections and hemorrhage, which could lead to mortality. Inflammation triggered by tissue damage can also lead to additional local or widespread tissue damage. The immune system is responsible for tissue repair and restoration, which is made more challenging when it is in the process of self-recovery. Because of these challenges, the Radiation and Nuclear Countermeasures Program (RNCP) and the Basic Immunology Branch (BIB) under the Division of Allergy, Immunology, and Transplantation (DAIT) within the National Institute of Allergy and Infectious Diseases (NIAID), along with partners from the Biomedical Advanced Research and Development Authority (BARDA), and the Radiation Injury Treatment Network (RITN) sponsored a two-day meeting titled Immune Dysfunction from Radiation Exposure held on September 9-10, 2020. The intent was to discuss the manifestations and mechanisms of radiation-induced immune dysfunction in people and animals, identify knowledge gaps, and discuss possible treatments to restore immune function and enhance tissue repair after irradiation.

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

In response to concerns over possible radiological or nuclear incidents, the Radiation and Nuclear Countermeasures Program within the National Institute of Allergy and Infectious Diseases (NIAID) was tasked by the U.S. Department of Health and Human Services to support development of medical countermeasures (MCM) to treat the acute and delayed injuries that can result from radiation exposure. To date, the only three drugs approved by the U.S. Food and Drug Administration for treatment of acute radiation syndrome are growth factors targeting granulocyte (Neupogen® or Neulasta®) or granulocyte and macrophage (Leukine®) hematopoietic cell lineages. Although these are currently stockpiled for deployment in response to a mass casualty scenario, these growth factors will likely be administered in a scarce-resources environment and availability may be limited. Therefore, there is growing interest in understanding the role that these growth factors play in mitigating radiation damage, to optimize their use and maximize the number of people who can be treated. For these reasons, the NIAID and the Radiation Injury Treatment Network organized a workshop to explore the use of growth factors and other cytokines as MCMs in the treatment of radiation-induced injuries. Subject matter experts from government, industry and academia gathered at this workshop to discuss the concept of operations, triage and treatment, administration to diverse civilian populations, growth factors under development for radiation indications, and how the practice of medicine can inform other potential approaches.

Use of Growth Factors and Other Cytokines for Treatment of Injuries During a Radiation Public Health Emergency.

Due to the threat of a radiological or nuclear incident that could impact citizens, the U.S. Department of Health and Human Services tasked the National Institute of Allergy and Infectious Diseases (NIAID) with identifying and funding early- to mid-stage medical countermeasure (MCM) development to treat radiation-induced injuries. Given that the body's natural response to radiation exposure includes production of growth factors and cytokines, and that the only drugs approved by the U.S. Food and Drug Administration to treat acute radiation syndrome are growth factors targeting either the granulocyte (Neupogen® or Neulasta®) or granulocyte and macrophage (Leukine®) hematopoietic cell lineages, there is interest in understanding the role that these factors play in responding to and/or ameliorating radiation damage. Furthermore, in an environment where resources are scarce, such as what might be expected during a radiation public health emergency, availability of growth factor or other treatments may be limited. For these reasons, the NIAID partnered with the Radiation Injury Treatment Network (RITN), whose membership includes medical centers with expertise in the management of bone marrow failure, to explore the use of growth factors and other cytokines as MCMs to mitigate/treat radiation injuries. A workshop was convened that included government, industry and academic subject matter experts, with presentations covering the anticipated concept of operations during a mass casualty incident including triage and treatment, growth factors under development for a radiation indication, and how the practice of medicine can inform other potential approaches, as well as considerations for administration of these products to diverse civilian populations. This report reviews the information presented, and provides an overview of the discussions from a guided breakout session.