Cytokine and Growth Factor Response in a Rat Model of Radiation Induced Injury to the Submental Muscles

ABSTRACT Submental muscles (i.e. mylohyoid and geniohyoid) play a vital role during swallowing, protecting the airway from ingested material. To design therapies to reduce the functional deficits associated with radiation treatment relies in part on our understanding of the changes in the cytokine and growth factor response that can impact muscle function. The purpose of this study is to quantify changes in the inflammatory, pro-fibrotic, and pro-angiogenic factors following 48Gy of fractionated radiation to the mylohyoid muscle. We hypothesized that (1) irradiation will provoke increases in TGF-1β and MMP-2 mRNA in the mylohyoid muscle; and (2) muscles surrounding the target location (i.e. geniohyoid and digastric muscles) will exhibit similar alterations in their gene expression profiles. Rats were exposed to 6 fractions of 8Gy using a 6MeV electron beam on a clinical linear accelerator. The highest dose curve was focused at the mylohyoid muscle. After 2-and 4-weeks post-radiation, the mylohyoid, geniohyoid, and digastric muscles were harvested. Expression of TNF-α, IFNγ, IL-1β, IL-6, TGF-1β, VEGF, MMP-2, and MMP-9 mRNA was analyzed via PCR and/or RT-PCR. TGF-1β, MMP-2, and IL-6 expression was upregulated in the irradiated mylohyoid compared to nonirradiated controls. No notable changes in TNF-α, IFNγ, and IL-1β mRNA expression was observed in irradiated muscles. Differing expression profiles were found in the surrounding muscles post-radiation. Results demonstrated that irradiation provokes molecular signals involved in the regulation of the extracellular matrix, which could lead to fibrosis or atrophy in the swallowing muscle after radiation.