Radioprotection of lungs by amifostine is associated with reduction in profibrogenic cytokine activity.
Radiation-induced pulmonary toxicity causes significant morbidity and mortality in patients irradiated for lung cancer, breast cancer, lymphoma or thymoma. Amifostine is an important drug in the emerging field of cytoprotection. Recent advances in our understanding of the mechanism of radiation-induced injury at the molecular and cellular levels have stimulated interest in the development of effective radioprotective strategies. Accumulation of macrophages with associated production of reactive oxygen species (ROS) and production and activation of cytokines is a key process involved in the pathophysiology of radiation injury in the lung. The purpose of this study was to determine whether the mechanism of radioprotection by amifostine includes reduction in both macrophage activity and the expression and activation of profibrogenic cytokines. Our results demonstrated a reduction in both functional and histological radiation-induced lung injury by amifostine. In addition, this study is the first to demonstrate that amifostine given prior to irradiation reduced both the accumulation of macrophages and the expression/activation of lung tissue Tgfb1 which was followed by the reduction of plasma Tgfb1 levels during the development of radiation-induced lung injury. Future studies are needed to determine whether administration of amifostine both during and after radiotherapy may further increase its radioprotective effect.
Vujaskovic
Zeljko
Z
Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710, USA. vujas@radonc.duke.edu
Feng
Qin-Fu
QF
Rabbani
Zahid N
ZN
Anscher
Mitchell S
MS
Samulski
Thaddeus V
TV
Brizel
David M
DM
D004999:Amifostine / Q000494:pharmacology*; D000818:Animals; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D053331:Ectodysplasins; D016326:Extracellular Matrix Proteins; D005260:Female; D008168:Lung / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology / Q000528:radiation effects*; D008565:Membrane Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D012119:Respiration / Q000187:drug effects / Q000528:radiation effects; D013997:Time Factors; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein
D004999:Amifostine; D003094:Collagen; D016207:Cytokines; D053331:Ectodysplasins; D016326:Extracellular Matrix Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D011837:Radiation-Protective Agents; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein