Evaluation of the effect of anti-interleukin-6 receptor antibodies on radiation-induced lung injury in a murine model

Radiation-induced lung injury (RILI) is the most significant dose-limiting toxicity of thoracic radiotherapy. In the acute phase, the clinical manifestation presents as radiation pneumonitis, for which corticosteroids are commonly used in treatment. The pathophysiology of the injury is believed to be mediated by immune responses and cytokines. This study aimed to evaluate the effect of an interleukin-6 receptor antibody (IL-6 RA), tocilizumab, on RILI in a preclinical in vivo experimental model. A total of 40 C57BL/6 mice were used to establish the experimental model. In the experimental group, mice received a single fraction of 20 Gy ionizing radiation (IR) to the right upper lung lobe, followed by administration of anti-mouse IL-6 RA on predetermined days. Five mice from each group were sacrificed on day 70 to assess early findings, while the remaining mice were sacrificed on day 150 to evaluate late-phase findings. Lung and skin tissues were evaluated histopathologically. Skin changes observed throughout the experiment were graded and recorded. When comparing the highest grades of radiation dermatitis observed during the study, it was found that mice receiving only IR experienced more severe skin toxicity than those treated with IL-6 RA (p = 0.005). Although the total lung injury scores in late-phase histopathological assessments of alveolar, peribronchiolar, perivascular, and interstitial areas were higher in the IR-only group, the difference was not statistically significant. Histopathological evaluation of the skin revealed that dermal fibrosis was more pronounced in the IR-only group compared to the IL-6 RA-treated group (p = 0.006). In this study, IL-6 RA administration in a murine model of RILI was associated with reduced signs of lung injury, although the difference did not reach statistical significance. While not the primary objective of the study, IL-6 RA was shown to have a protective and therapeutic effect against radiation- induced skin injury. These findings suggest that the efficacy of tocilizumab in managing radiotherapy-associated skin toxicity should be further evaluated in clinical trials.