Relationship between cytokines and brain-derived neurotrophic factor (BDNF) in trajectories of cancer-related cognitive impairment

Cytokine. 2021 Aug:144:155556. doi: 10.1016/j.cyto.2021.155556. Epub 2021 May 10.


Cytokines facilitate the peripheral immune and cerebral response, through their ability to modulate the expression of brain derived neurotrophic factor (BDNF). Cytokines and BDNF are implicated in cancer-related cognitive impairment (CRCI), but their relationship has not been clearly defined for this condition. The aim of this study was to evaluate the associations of cytokines and BDNF among early stage breast cancer (ESBC) patients with different CRCI trajectories. This was a multicenter longitudinal study involving 136 ESBC patients. CRCI was assessed using the FACT-Cog (V3) questionnaire. Plasma cytokines and BDNF levels were quantified at three time points throughout chemotherapy. The associations between cytokines and BDNF were analyzed using linear mixed models, with interaction terms for CRCI status. All cytokines analyzed showed inverse associations with BDNF levels. There was a significant interaction between IL-6 and the persistent impairment trajectory, which would impact on BDNF levels (p = 0.026). The inverse associations with BDNF were more pronounced for IFN-γ, IL-1β, IL-4, IL-8, and GM-CSF in patients with persistent CRCI. The coefficient values for IL-2, IL-4, and TNF-α also indicate that there was a greater magnitude of decrease in BDNF level for every unit of cytokine increase in patients with acute and persistent CRCI, compared to patients without CRCI. The differential associations between cytokines and BDNF may be indicative of probable susceptibility to the elevation of cytokines. Further research is required to elucidate the specific associations of cytokines and BDNF, along with their contributions to acute and persistent CRCI.

Keywords: BDNF; Breast cancer; Cancer-related cognitive impairment; Cytokines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain-Derived Neurotrophic Factor / blood*
  • Breast Neoplasms / blood*
  • Cognitive Dysfunction / blood*
  • Cytokines / blood*
  • Female
  • Humans
  • Longitudinal Studies
  • Middle Aged
  • Prospective Studies


  • Brain-Derived Neurotrophic Factor
  • Cytokines
  • BDNF protein, human