Differential associations of proinflammatory and anti-inflammatory cytokines with depression severity from noncancer status to breast cancer course and subsequent chemotherapy.

BACKGROUND: In this study, we examined the differential associations of various proinflammatory and anti-inflammatory cytokines with depression severity from the development of breast cancer to subsequent chemotherapy treatment. METHODS: A cross-sectional study was conducted on a sample of 116 women: 29 controls without cancer, 55 patients with breast cancer who were not receiving chemotherapy, and 32 patients with breast cancer who were receiving chemotherapy. Blood samples were assayed to evaluate serum levels of the following cytokines: interferon-γ, interleukin (IL)-12 (p70), IL-1ß, IL-2, tumor necrosis factor (TNF)-α, IL-4, IL-5, IL-10, IL-13, IL-6, and IL-17A. Depression severity was assessed using the Patient Health Questionnaire. RESULTS: After adjustment for sociodemographics, consistent patterns of the association between cytokine and depression were noted in the different groups. No significant associations were observed in the controls. Inverse associations were observed between cytokines levels and depression severity in patients with breast cancer who were not receiving chemotherapy, whereas positive associations were noted in patients with breast cancer who were receiving chemotherapy. Specific differential relationships between IL-5 levels and depression severity were found between patients with breast cancer who were receiving and not receiving chemotherapy. CONCLUSIONS: Our study revealed differential relationships between cytokine levels and depression severity with the development of cancer. Immunostimulation and immunosuppression in breast cancer and cancer treatment may account for the differential responses with the development of breast cancer.

Circulating cytokines as predictors of depression in patients with breast cancer.

Depression is a common comorbid disorder associated with breast cancer, and it can have considerable physical and psychological impacts. Circulating cytokines have been proposed as a potential tool to predict depression in various diseases; however, limited studies have specifically examined it in breast cancer. In this study, we examined and compared the prediction ability of various circulating cytokines for depression in patients with breast cancer. Eighty-three patients with a new diagnosis of breast cancer not receiving chemotherapy were recruited; among them, 15 patients had depression and 68 did not have depression. Depression was evaluated using the Patient Health Questionnaire 9 (PHQ-9). Cytokine levels in the serum were measured using an immunology multiplex assay. Two types of cytokines were assayed: (1) proinflammatory cytokines (interleukin [IL]-1ß, IL-2, IL-6, IL-12, IL-17A, interferon [IFN]γ, and tumor necrosis factor [TNF]α) and (2) anti-inflammatory cytokines (IL-4, IL-5, IL-10, and IL-13). Receiver operating characteristic (ROC) analysis was performed to calculate the area under the curves (AUCs), sensitivities, and specificities of circulating cytokines for predicting depression. As a result, IL-2 (AUC = 0.78) and IL-5 (AUC = 0.76) demonstrated good predictability for depression, even after controlling for the covariates (i.e. age, education, stage of cancer, surgery, radiation therapy, and hormone therapy). The optimal cut-off value of IL-2 for predicting depression was 1.06 pg/mL with a sensitivity of 86.7% and a specificity of 52.9%; this cytokine also had the best prediction ability in this study. Owing to the prediction ability and practical feasibility of circulating cytokines, they may be used as a valid laboratory diagnostic tool for depression in breast cancer.