P. Monti

Abdominal Radiation Exposure Elicits Inflammatory Responses and Abscopal Effects in the Lungs of Mice

Abstract Van der Meeren, A., Monti, P., Vandamme, M., Squiban, C., Wysocki, J. and Griffiths, N. Abdominal Radiation Exposure Elicits Inflammatory Responses and Abscopal Effects in the Lungs of Mice. Radiat. Res. 163, 144–152 (2005). An inflammatory reaction is a classical feature of radiation exposure and appears to be a key event in the development of the acute radiation syndrome. We have investigated the radiation-induced inflammatory response in C57BL6/J mice after total abdominal or total-body irradiation at a dose of 15 Gy. Our goal was to determine the radiation-induced inflammatory response of the gut and to study the consequences of abdominal irradiation for the intestine and for the lungs as a distant organ. A comparison with total-body irradiation was used to take into account the hematopoietic response in the inflammatory process. For both irradiation regimens, systemic and intestinal responses were evaluated. A systemic inflammatory reaction was found after abdominal and total-body irradiation, concomitant with increased cytokine and chemokine production in the jejunum of irradiated mice. In the lungs, the radiation-induced changes in the production of cytokines and chemokines and in the expression of adhesion molecules after both abdominal and total-body irradiation indicate a possible abscopal effect of radiation in our model. The effects observed in the lungs after irradiation of the abdomino-pelvic region may be caused by circulating inflammatory mediators consequent to the gut inflammatory response.

Characterization of the acute inflammatory response after irradiation in mice and its regulation by interleukin 4 (Il4).

Abstract Van der Meeren, A., Monti, P., Lebaron-Jacobs, L., Marquette, C. and Gourmelon, P. Characterization of the Acute Inflammatory Response after Irradiation in Mice and its Regulation by Interleukin 4 (Il4). Radiat. Res. 155, 856–863 (2001). The aim of this study was to determine the effects of total-body irradiation of mice on the acute release of a panel of several mediators of inflammation and to evaluate the efficacy of Il4 in regulating these radiation-induced modifications. We studied the effects of exposure of C57BL6/J mice to 8 Gy γ rays on the early release of cytokines, chemokines, acute-phase proteins, prostaglandins and corticosterone in either plasma or tissues compared to those observed after intraperitoneal injection of lipopolysaccharide from 1 h to 3 days after stimulation. During the characterization of the acute inflammatory response induced by radiation or lipopolysaccharide, we observed differences both in the type of mediators produced and in the time course of release. We next determined the anti-inflammatory potential of Il4 in this model of total-body irradiation. We found that Il4 was able to down-regulate the radiation-induced production of mediators of inflammation such as Gro1 (also known as KC, N51) in plasma and lung, corticosterone in blood, Il1b in lung, and prostaglandin E2 in colon, suggesting the anti-inflammatory potential of Il4 in regulating the radiation-induced response.

Whole-body gamma irradiation modifies bile composition in the pig.

The effects of 6 Gy whole-body 60Co gamma irradiation on bile composition in pigs were studied to determine possible alterations in the quality of the bile, which may be a determining factor in diarrhea as well as nutrient malabsorption, which classically occurs after irradiation. The bile duct of pigs was catheterized to allow a total and continuous deviation of bile over several weeks, before and after irradiation. After measurement of the volume and sampling, bile was returned to the animal via a duodenal catheter. Bile samples were then analyzed for cholesterol, phospholipid and total bile acid content. Individual bile acids were quantified by HPLC analysis. Bile flow was significantly decreased during the first 24 h and after the fifth day postirradiation. Whereas cholesterol, phospholipid and total bile acid concentrations were not altered, profiles of individual bile acids were modified significantly as early as the first day postirradiation. Moreover, the change of these profiles with time was specific for each bile acid. Such modifications in bile acid profiles resulted in a change in the properties of the bile acid pool in an increased proportion of dihydroxylated bile acids known to interfere with gut functions, and it is reasonable to suggest that radiation-induced changes in bile acid profiles may be involved in radiation-induced gastrointestinal disorders.