The role of proinflammatory cytokines in the development of anthracycline-induced heart failure

Objective. To study the pathogenetic and prognostic role of cytokines (tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β)) in the development of anthracycline-induced chronic heart failure (CHF).Material and Methods. A total of 176 women with breast cancer who received anthracycline antibiotics as a part of polychemotherapy regimens were examined. Upon examination, the patients in remission were divided into two groups within 12 months after the completion of chemotherapy: patients with the development of cardiotoxic remodeling (group 1, n = 52) and women with preserved cardiac function (group 2, n = 124). All patients received echocardiography study before, during, and after chemotherapy. Biochemical blood tests were done to determine the levels of TNF-α and IL-1β before chemotherapy, immediately after it, and 12 months after chemotherapy completion. Determination of polymorphisms of the TNF-α (-308G/A, rs1800629) and IL-1β genes (+3953, rs1143634) was carried out by polymerization chain reaction.Results. A higher level of TNF-α and IL-1β in group 1 was associated with the development of heart failure 12 months after the end of chemotherapy. The level of TNF-α over 7.5 pg/mL after the completion of chemotherapy allowed to predict the development of cardiovascular complications in women receiving anthracycline therapy with sensitivity of 44.2% and specificity of 75.8% (AUS = 0.600; 95% CI = 0.524-0.673; p = 0.035). The study did not reveal any significant differences in the frequency distribution for genotypes of 308G/A polymorphism (rs1800629) of the TNF-α gene and +3953 (rs1143634) polymorphism of the IL-1β gene in the studied groups.Conclusion. Patients with breast cancer who developed anthracycline-induced heart failure 12 months after the end of chemotherapy had the increased levels of TNF-α and IL-1β suggesting the pathogenetic role of proinflammatory cytokines in the development of cardiac injury during anthracycline therapy.