Patients with cancer often complain of cognitive problems during their treatment and chemotherapy-related cognitive impairment (CRCI) remains an important clinical issue in such patients. CRCI also known as ‘chemobrain’, occurs in 17–75% of patients with various malignancies treated with chemotherapeutic agents that worsen the quality of life. Depression is one of the most prevalent psychological symptoms perceived by cancer patients. It worsens during chemotherapy, persists for a long time after the end of chemotherapy, is also manifested in the recurrence of the disease and finally consists an independent prognostic factor for mortality. Depression leads to a poorer quality of life (QOL) and compromises patient outcomes, with depression resulting in higher rates of mortality in cancer.

Cytokine dysregulation is thought to play an important role in the pathogenesis of CRCI. Chemotherapy can induce an immune reaction that subsequently causes highly elevated levels of various cytokines via a positive feedback loop between cytokines and white blood cells. Small quantities of chemotherapeutic drugs can cross the blood-brain barrier and enter the brain, resulting in overproduction of pro-inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-α(TNF-α), and suppression of anti-inflammatory cytokines, such as IL-4 and IL-10. Pro-inflammatory cytokines elicited by chemotherapy of peripheral normal and tumor tissues also can cross the blood-brain barrier, damage neuronal cells in the brain, and disrupt the blood-brain barrier integrity and transport mechanisms, further leading to the overflow of chemotherapeutic drugs into the brain. Pro-inflammatory cytokines have considerable toxic effects on neuronal cells, particularly those in the hippocampus and the pre-frontal cortex associated with cognitive functions, as they are more susceptible to neurotoxin insults. Existing evidence suggests that inflammatory cytokines increases during chemotherapy which plays an intermediary role in CRCI. Several clinical studies have revealed that higher blood concentration of IL-6 is associated with poorer cognitive performance, but the elevated level of IL-4 is protective against chemobrain in breast cancer patients. A similar study conducted in our centre has also demonstrated the occurrence of cognitive impairment after chemotherapy administration in lymphoma patients. These studies have led to the hypothesis that chemotherapy-induced cytokine dysregulation and disrupted neuroplasticity in related brain regions may lead to the development of CRCI. This intermediary role of cytokines in CRCI is still controversial and requires further evaluation.