Play a major role in Z-VAD-FMK subsequent radiation induced lung toxicity b1, interleukin -6 and IL-10 during RT have been suggested as possible risk markers in these studies. However, other studies have reported contradictory or negative findings. The rationale for the composition of our panel of 22 potential biomarkers for lung tissue toxicity was based on several published reports dissecting inflammatory and radiation response. The plasma levels of a range of cytokines have been previously investigated in context of both murine and cell models. A range of pro-inflammatory cytokines are expressed as acute phase reactants, including tumour necrosis factor -a, i IL-1 and IL6. Chemokines act as chemoattractants for leukocytes which potentiate the inflammatory response, such as interferoninducible protein-10 which attracts predominantly neutrophils, macrophage inflammatory protein -1a, and macrophage chemoattractant protein -3 which attracts predominantly monocytes, and MIP-1b and MIP-3a which attract predominantly lymphocytes. Induction of MIP-3b results in chemoattraction of dendritic cells and antigen engaged B-cells. MCP-1 is a cytokine that has been associated with many inflammation-related diseases and has been implicated in the progression and prognosis of several cancers. Upregulation of MCP-3 gene expression has been shown to be maximal at 1hour in response to radiation in rat liver. Excessive release of interferon-gamma has been associated with the pathogenesis of chronic inflammatory and autoimmune diseases. Macrophage-derived chemokine, is involved in chronic inflammation and dendritic cell and lymphocyte homing. Eotaxin is a chemoattractant for eosinophils and is implicated in acute inflammatory lung injury responses, particularly in emphysema and asthma. IL-3, IL-11, IL-22 and IL-33 are all acute phase reactants that potentiate cellular immune signalling and inflammatory responses. The induction of all these inflammatory cytokines in response to radiation stimulate the subsequent expression of fibrotic cytokines such as the TGF-b family and vascular endothelial growth factor. These in turn facilitate the progression from pneumonitis to lung fibrosis. Helping to balance this process, both IL-22 and IL-10 can act to down-regulate the pneumonitic response by blocking proinflammatory cytokines and function of antigen-presenting cells. Additionally, tissue inhibitors of metalloproteinase -1 acts to down-regulate the profibrotic response and is elevated in chronic inflammatory disease states. In this study, we report the modulation of plasma concentrations of these cytokines in patients receiving RT alone or RT with concurrent radiosensitising chemotherapy. In contrast to many previous studies, we consider the differential patterns of response in patients receiving radiosensitizing chemotherapy compared to those receiving RT alone. We assess a homogenous cohort of patients receiving identical dose/fractionation schedules, and employ a large panel of candidate cytokines. Additionally, we report the effect of treatment volume and dose to normal lung tissue on plasma cytokine concentrations, suggesting that these cytokines could be used as in-vivo ‘biodosimeters’ of individual radiation dose.