Radiation Induced Inflammation

1.4 Radiation-induced inflammation

Ionising radiation causes liver inflammation and injury, and a significant increase in the number of non-parenchymal liver cells has been reported following irradiation (Geraci and Mariano 1993). It is essential to explore the molecular mechanisms underlying the leukocyte transmigration processes to gain an understanding of the inflammatory disorders associated with RILD. Alcoholic liver disease, viral hepatitis and nonalcoholic steatohepatitis are the most common hepatic disorders that harbour risks of fibrosis and the development of cirrhosis (Fig. 2). These disorders are directly associated with persistent inflammation and the harmful substances that are produced as a consequence of oxidative stress, and

The classic signs of inflammation are heat, redness, pain and swelling (Butterfield et al. 2006; Rocha e Silva 1978). Inflammation is a multistep process that can be activated by diverse stimuli and factors that include physical, mechanical or thermal stresses, or the invasion of the body by microorganisms. Inflammation follows a defined order of events irrespective of the causative factor (Butterfield et al. 2006). It includes the flow of particular signalling sequences from specific cells that activate other groups of cells, and that activate and recruit white blood cells (WBC) into the stressed or injured area, which is an important step in the inflammatory cascade. Among the WBC, the neutrophils represent the first line of defence (Butterfield et al. 2006; Cannon and St Pierre

2001). The hepatocellular stress that is induced by irradiation or other toxins may activate the resident macrophages on one side and proinflammatory mediator release on the other side (Ramadori et al. 2008), and these cytokines play major roles in modulating the liver’s response (Streetz et al. 2001). Upon hepatic stimulation, the cells within the inflammatory infiltrate produce cytokines, and these are known to be the hepatic modulators. The induction of these cytokines leads to the consecutive production of further inflammatory mediators and adhesion molecules (Rogler and Andus 1998). The early induction of the proinflammatory cytokines and of adhesion molecules following gamma irradiation has been reported (Christiansen et al. 2007b; Moriconi et al. 2009). Similarly, prompt increases in the tissue concentrations of these mediators after irradiation facilitate the transmigration of the inflammatory cells towards the target. Leukocytes may enter the liver tissue through the portal tract where the inflammation has been initiated (Ramadori et al.