Therapies for Radiation Injuries: Research Perspectives

Abstract

Exposure to radiation damages the immune, hematopoietic, and gastrointestinal components of the host defense system. This may lead to serious endogenous or exogenous infections. When radiation injury is combined with other physical trauma, e.g., burn or wound, the resulting damage to these systems is synergistic, and treatment for infection requires multiple approaches. This paper reviews successful single and combined therapeutic modalities for infections in irradiated mice and irradiated mice inflicted with trauma that are currently conducted at the Armed Forces Radiobiology Research Institute. The models of endogenous and exogenous infection and combined injury are described. The management of wounds infected with bacteria, exogenous systemic infection due to gram-negative enteric bacteria, and the chemoprophylaxis of enteric-derived systemic infection with quinolones is described. Infections can be treated successfully with proper antimicrobial therapy. In gamma- and neutron-irradiated mice, the immunomodulator trehalose dimycolate (TDM) was effective in treating endogenous infection. TDM with the antimicrobial ceftriaxone was effective in treating exogenous infection due to Klebsiella pneumoniae. Improvement in managing infection in irradiated and injured hosts will require further research using these diagnostic and therapeutic modalities. Accurate biological dosimetry is critical in determining if victims are at risk of developing infection. We found that radiation induced changes in plasma diamine oxidase activity; monitoring these changes was a useful indicator of the severity of radiation injury.

A novel therapy, using Ghrelin with pegylated G-CSF, inhibits brain hemorrhage from ionizing radiation or combined radiation injury

“…Ultimately, impairment of sensitive tissues that sustain crucial immunochemical and metabolic homeostasis, breach of biological barriers, and post-irradiation sepsis leads to multiple organ failure (MOF). [4][5][6][7][8][9][10][11][12] Animal studies from literature clearly indicate that wounds, [13][14][15] burns, [15][16][17] sepsis, 18 and/or hemorrhage 19 aggravate ARS, particularly in CI. Similar observations were found in humans exposed to ionizing radiation and burn trauma.…”

“…Animal studies from literature clearly indicate that wounds, 13 – 15 burns, 15 – 17 sepsis, 18 and/or hemorrhage 19 aggravate ARS, particularly in CI. Similar observations were found in humans exposed to ionizing radiation and burn trauma.…”

Immune System Phenotyping of Radiation and Radiation Combined Injury in Outbred Mice

“…Individual outcomes of such a disaster will be further complicated by variable radiation exposures and differing severity of injuries. The levels of susceptibility to opportunistic infection will depend on the level of radiation exposure and combined injury (4, 5). Currently, no effective treatments to achieve protection from secondary infections after RCI exist, partially due to a lack of understanding of the immunological sequelae encountered after RCI.…”

Decreasing the Adverse Effects in Pelvic Radiation Therapy: A Randomized Controlled Trial Evaluating the Use of Probiotics

“…Antibiotics have been used in human clinical trials to manipulate the radiosensitivity of the intestine, but no clearly effective protocol has emerged. 15 …”