Impact of Elevated Circulating Histones on Systemic Inflammation after Radiofrequency Ablation in Lung Cancer Patients

BACKGROUND: This study investigated the changes of circulating histones following radiofrequency ablation (RFA) in lung cancer patients and their impact on systemic inflammation. METHODS: Serial blood samples were obtained from a total of 65 primary and metastatic lung cancer patients undergoing RFA at 2 time points: pre-RFA and post-RFA within 48 h. Circulating histones, myeloperoxidase (MPO), and multiple inflammatory cytokines were measured. Moreover, the patient's sera were incubated overnight with human monocytic U937 cells in the presence or absence of anti-histone antibody, and cytokine production was evaluated. RESULTS: Compared to pre-RFA, there was a significant increase in circulating histones within 48 h after RFA, along with an elevation of MPO and several canonical inflammatory cytokines. Circulating histones were correlated with these inflammatory markers. Notably, compared to the sera obtained before RFA, the patients' post-RFA sera significantly stimulated cytokine production in the supernatant of U937 cells, which could be prevented by anti-histone antibody, thereby confirming a cause-effect relationship between circulating histones and systemic inflammation. CONCLUSIONS: This study showed that circulating histones may serve as a marker indicating RFA-related systemic inflammation as well as represent a therapeutic target for resolution of inflammation.