Fibrosis and cytokine mechanisms: relevant in hadron therapy?

Cytokines are important for signalling between cells and tissues and constitute a humoral component of the response of cells and tissues to radiotherapy. Although several cytokines have been implicated in mediating radiation-induced reactions of normal tissues to both conventional photon and heavy ion irradiation, the mechanisms are only beginning to be elucidated.

Published and own data on radiation-induced cytokine expression from cell culture and clinical studies are reviewed. Current models of cytokine-mediated multicellular interactions in radiation-induced reactions are presented.

The major cytokines in the radiation response of non-hemopoietic tissues include IL-6, IL-1, TNF-alpha and TGF-beta. Different cell types interact via cytokines in a complex network of effector and receptor cells, including inflammatory cells, tissue-specific functional cells and fibroblasts. TGF-beta appears to be of particular importance in the development of late reactions to radiation therapy, such as fibrosis, in response to both conventional therapy as well as hadron therapy.