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

Author:

Teplyakov A. T.1ORCID,Shilov S. N.2ORCID,Popova A. A.2ORCID,Berezikova E. N.2ORCID,Grakova E. V.1ORCID,Neupokoeva M. N.2ORCID,Kopeva K. V.1ORCID,Ratushnyak E. T.3ORCID,Stepachev E. I.2ORCID

Affiliation:

1. Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences

2. Novosibirsk State Medical University

3. State Novosibirsk Regional Medical and Physical Education Dispensary

Abstract

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. 

Publisher

Cardiology Research Institute

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