Variation of inflammatory mediators during fractionated γ-radiation in the colonic mucosa of rat.
O. Gremy, C. Linard, M. Benderitter, 4th European mucosal immunology group meeting, 8-10/10/2004, Lyon.
Despite the use of fractionated radiotherapy to treat abdominal tumors, some patients contract an intestinal inflammation called enteritis. A rat model of fractionated colo-rectal irradiation (up to 9 doses of 5Gy delivered 3 times a week) was implemented to investigate the pattern of some cytokines, chemokines and nuclear factors in response to g-rays. 24 hours after 20Gy and 45Gy cumulated doses of irradiation, mRNA expression of genes involved in inflammation was examined in the terminal colonic mucosa by real-time PCR. Neutrophils recruitment was characterized by myeloperoxidase immunohistochemistry. At 20Gy, the PPAR-α mRNA level revealed a drastic depression (p<0.001) and remained nearly non-existent at 45Gy. IL-1β expression showed a significant increase (>4-fold, p<0.005) and tended to maintain a level of 2-fold control value for 45Gy. The neutrophil chemoattractant CINC expression tended to go up and increased 2.5-fold (p<0.05) with 45Gy, corroborated by a neutrophils recruitment. The MCP-1 mRNA level increased 7.5-fold (p<0.005) at 45 Gy. At 20Gy, IL-10 expression was comparable to controls whereas was 3 times as low at 45Gy (p<0.05). NFκB p65 is known for regulating pro-inflammatory cytokines. At 20Gy, its transcription slightly increased (1.5-fold) then remained stable at 45 Gy. Unexpectedly, IFN-g transcription rapidly declined (>5-fold) with 20Gy then reached a normal level at 45Gy. Moreover, IL-6 barely showed any variation. Fractionated irradiation upset in vivo the balance of the pro/anti-inflammatory actors. The pattern of cytokines changed during this protocol, resulting in a repression of anti-inflammatory mediators (PPAR-α, IL-10) and an over-expression of the pro-inflammatory chemokines (CINC, MCP-1).