PARENT SESSION

Radiation Signaling in Normal Tissues

(MS039) An investigation into the relationship between IL-1, IL-1, MCP-1, and radiation late effects in the lung.

Williams, Jacqueline^*,1, Hernady, Eric¹, Johnston, Carl², Reed, Christina², Finkelstein, Jacob², ¹ Radiation Oncology, Rochester, NY, USA² Pediatrics/Neonatology, Rochester, NY, USA

ABSTRACT- Inflammation plays a significant role in normal lung response to radiation. In the pneumonitic phase, monocyte recruitment results from the production of chemoattractants, with endothelial cell expression of MCP-1 playing an important role; this expression is induced by IL-1. Indeed, both IL-1 and IL-1 are important in the development of acute and chronic inflammation, although they appear to exist in balance and may play a differential role in injury progression. Reduced lung pathology in irradiated IL-1R1-/- animals supports a critical role for the IL-1 pathway, but does not differentiate between the two interleukins. We hypothesize that production of MCP-1 is by an autocrine loop through IL-1, regulated by IL-1. Using our whole lung radiation model with specific gene ablation and chimera animals, we examined the interactions between IL-1, IL-1, and MCP-1 expression, correlating these with cell recruitment and an endpoint of radiation fibrosis. To address the role of IL-1, we irradiated groups of IL-1-/- mice using 12.5 Gy thoracic irradiation. In addition, we utilized chimera technology to assess the relative roles of IL-1 and MCP-1 expression in recruited inflammatory cells versus the parenchyma. Once engraftment was proven, mice were exposed to thoracic irradiation (0, 12.5 Gy). Animals from all studies were sacrificed at 10, 16, 26 or 32 weeks post-irradiation. At these times, lungs underwent BAL and cell differentials were made. Lungs were also taken for mRNA and protein analysis, and sections underwent processing followed by image analysis. Early results are suggesting a significant decrease in both proinflammatory and chemokine expression in the knockout animals and the chimeric models. This is supported by a less reactive pathology. Results from early time points support our hypothesis that IL-1 plays a critical regulatory role in the initiation of cell recruitment as part of the pneumonitic phase. Supported by NIH P01 HL71659.

Key words: lung, interleukin-1, MCP-1