Interleukin-10 Levels are Associated with Doxorubicin-Related Cardiotoxicity in Breast Cancer Patients in a One-Year Follow-Up Study

Immunol Invest. 2022 May;51(4):883-898. doi: 10.1080/08820139.2021.1882486. Epub 2021 Feb 9.

Abstract

Background: Myocardial toxicity is a common side effect of doxorubicin (DOXO) therapy in breast cancer patients. We hypothesized that DOXO-induced cardiotoxicity may be related to the release of inflammatory cytokines in response to the treatment. This study aimed to assess changes in plasma levels of interleukin (IL)-1β, IL-6, IL-10 and tumor necrosis factor (TNF) after chemotherapy and to correlate these levels with cardiac biomarkers and clinical data.

Methods: Sixty-four patients with breast cancer treated with DOXO were included. Twenty-two subjects (cases) developed cardiotoxicity until one year after the end of DOXO treatment. Cytokines and cardiac markers were evaluated before starting chemotherapy (T0), up to 7 days after the last infusion (T1) and 12 months after the last infusion (T2).

Results: Higher IL-10 levels were observed in the case group compared to controls at T1 (p = .006) and T2 (p = .046). The IL-1β, IL-6 and TNF levels did not change during treatment in each group (p > .05), nor between the case and control groups. The IL-10 levels were higher at T1 than at T0 and T2 (p < .05 for both) in the cardiotoxicity group. A correlation between IL-10 and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels at T0 and T2 in the cardiotoxicity group was observed (p = .048 and p = .004, respectively).

Conclusion: Our study demonstrated that DOXO induced an increase in plasma IL-10 levels in patients who presented cardiotoxicity after treatment, which correlated with NT-proBNP levels.

Keywords: Breast cancer; cardiotoxicity; chemotherapy; cytokine; doxorrubicin.

MeSH terms

  • Biomarkers
  • Breast Neoplasms* / drug therapy
  • Cardiotoxicity* / etiology
  • Doxorubicin / adverse effects
  • Female
  • Follow-Up Studies
  • Humans
  • Interleukin-10* / blood
  • Natriuretic Peptide, Brain / blood
  • Peptide Fragments / blood

Substances

  • Biomarkers
  • Peptide Fragments
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • Interleukin-10
  • Doxorubicin