Inflammation and Immunity in Radiation Damage to the Gut Mucosa

Abstract

Erythema was observed on the skin of the first patients treated with radiation therapy. It is in particular to reduce this erythema, one feature of tissue inflammation, that prescribed dose to the tumor site started to be fractionated. It is now well known that radiation exposure of normal tissues generates a sustained and apparently uncontrolled inflammatory process. Radiation-induced inflammation is always observed, often described, sometimes partly explained, but still today far from being completely understood. The thing with the gut and especially the gut mucosa is that it is at the frontier between the external milieu and the organism, is in contact with a plethora of commensal and foreign antigens, possesses a dense-associated lymphoid tissue, and is particularly radiation sensitive because of a high mucosal turnover rate. All these characteristics make the gut mucosa a strong responsive organ in terms of radiation-induced immunoinflammation. This paper will focus on what has been observed in the normal gut and what remains to be done concerning the immunoinflammatory response following localized radiation exposure.

Key role for neutrophils in radiation-induced antitumor immune responses: Potentiation with G-CSF

“…The hallmark of sterile inflammation is the rapid infiltration of neutrophils, as is also observed in the spleen, thymus, and gut after whole-body ionizing radiation in mice (12)(13)(14). Inflammatory responses, known as damage-associated molecular patterns (DAMPs), which are released from dying cells, are initiated by endogenous molecules (10,15,16).…”

Reducing radiation-induced gastrointestinal toxicity — the role of the PHD/HIF axis

“…For example, when radiotherapy treatment is used to treat bladder or prostate cancer, it is often difficult to spare areas of the gastrointestinal (GI) tract, resulting in radiation-induced GI toxicity. Furthermore, patients with abdominal or head and neck tumors have a reasonable prognosis following treatment, making delayed toxic side effects a problem for a significant proportion of long-term survivors (2,3).…”

“…The effects of radiation-induced normal tissue toxicity vary depending on the type of tissue being irradiated, the volume of tissue receiving irradiation, and the dose and dose rate delivered (3). Toxicity can result in symptoms ranging from mild or moderate to life threatening.…”

“…Neutrophils that infiltrate the damaged tissue can also release factors that lead to further circulating monocyte recruitment, highlighting the crosstalk between cell types. In addition to responding to the initial damage by mounting an inflammatory response, macrophages also help resolve tissue damage by facilitating the removal of apoptotic bacteria, cellular debris, and neutrophils (3,34). The role of neutrophils in responding to radiation-induced GI toxicity is not fully understood.…”

“…The role of neutrophils in responding to radiation-induced GI toxicity is not fully understood. On one hand, ROS produced by neutrophils are likely important in the response to inflammation and infection following breakdown of the mucosal and vascular barriers (3). On the other hand, chronic generation of ROS may contribute to the late effects of radiation on normal tissue such as a fibro-atrophic process (35).…”