The Measurements of Plasma Cytokines in Radiation-induced Pneumonitis in Lung Cancer Patients

摘要

PURPOSE: To investigate whether changes in plasma concentrations of transforming growth factor-beta1 (TGF-beta1), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) could be used to identify the development of radiation-induced pneumonitis in the lung cancer patients. METHODS AND MATERIALS: Seventeen patients with lung cancer (11 NSCLC, 6 SCLC) were enrolled in a prospective study designed to evaluate clinical and molecular biologic correlation of radiation-induced pneumonitis. The study began in May 1998 and completed in July 1999. All patients were treated with radiotherapy with curative intent : 1.8 Gy per day, 5 fractions per week. Serial measurements of plasma TGF-beta1, TNF-alpha and IL-6 were obtained in all patients before, weekly during radiotherapy and at each follow-up visits after completion of treatment. These measurements were quantified using enzyme linked immunosorbent assay (ELISA). All patients were evaluated for signs and symptoms of pneumonitis at each follow-up visit after completion of radiotherapy. High resolution CT (HRCT) scans were obtained when signs and symptoms of pneumonitis were developed after completion of radiotherapy. RESULTS: Thirteen patients eventually developed signs and symptoms of clinical pneumonitis while four patients did not. TGF-beta1 levels were elevated in all 13 patients with pneumonitis, which showed characteristic pattern of elevation (38.45 ng/ml at pretreatment, 13.66 ng/ml during radiotherapy, then 60.63 ng/ml at 2-4 weeks after completion of radiotherapy). The levels of TNF-alpha and IL-6 were also elevated in the group of patients who developed pneumonitis but the pattern was not characteristic. CONCLUSIONS: Changes in plasma TGFbeta-1 levels before, during and after radiotherapy appears to be a useful means by which to identify patients at risk for the development of symptomatic pneumonitis. Other cytokines like TNF-alpha and IL-6 shows no meaningful changes in association with radiation pneumonitis.