OBJECTIVE: Aim: To analyze the role of cytokines in the progression of heart failure (HF) in patients with concomitant pathology of the thyroid gland.
METHODS: Materials and Methods: The systematization of literature data on the role of cytokines in the progression of HF in patients with concomitant thyroid pathology (TP) was carried out. The results of our own research were presented.
CONCLUSIONS: Conclusions: The final chapter in the history of the role of cytokines in the progression of HF has not yet been written. Further studies, including genetic ones, are necessary. The patients with HF have higher levels of TNFβ and IL-6, and a lower concentration of IL-4, compared to the control group. Patients with a fatal outcome of the disease, in contrast to those who survived for two years, have an increased level of TNFβ. In patients with concomitant TP, who had repeated hospitalization, a lower level was registered, compared to that under conditions of a more favorable course of heart failure. Concentrations of cytokines in the blood of patients with HF are associated with gene polymorphisms of the β-adrenoreceptor system: the C-allele of the Gly389A polymorphism of the β1-adrenoceptor gene leads to a decrease in the risk of increasing TNFα; IL-1α increases in the presence of the A-allele of the Ser49Gly polymorphism of this gene. In patients with HF and concomitant thyroid pathology, the risk of IL-6 growth increases in homozygous (C) patients for the Ser275 polymorphism of the β3 subunit of the G-protein.

Heart failure (HF) and multiple HF-related phenotypes are heritable. Genes implicated in the HF pathophysiology would be expected to influence the response to treatment.
We conducted a series of systematic literature searches on the pharmacogenetics of HF therapy to assess the current knowledge on this field.
Existing data related to HF pharmacogenomics are still limited. The ADRB1 gene is a likely candidate to predict response to β-blockers. Moreover, the cytochrome P450 2D6 coding gene (CYP2D6) clearly affects the pharmacokinetics of metoprolol, although the clinical impact of this association remains to be established.
Given the rising prevalence of HF and related costs, a more personalized use of HF drugs could have a remarkable benefit for patients, caregivers and healthcare systems.

The extent of blood pressure lowering by anti-hypertensive agents is difficult to predict for individual patients, even when evaluated in the context of biochemical or demographic information. Genetic predictors (mainly single nucleotide polymorphisms, SNPs) have been the focus of several recent studies and are gaining much attention. We have conducted a literature search for studies in which the lowering of ambient blood pressure by specific drugs or drug classes in humans was related to specific genotypes. Twenty-eight studies were identified, of which six had a single-dose design, and the remaining 22 studied drug effects after more than 4 weeks of drug administration. Virtually all were association studies. Prospective trials that compared the prognostic value of genetic methods to routine clinical practice were not identified. Almost all studies used a candidate-gene design, usually with a very small number of SNPs (typically one). Gene-gene and gene-environment interactions were studied only rarely. Only one study targeted genes involved in drug metabolism. Most candidate-genes were part of the renin-angiotensin system. By far the most extensively studied has been the angiotensin-converting enzyme insertion/deletion polymorphism (15 studies) but, to date, no clear picture has emerged for this or other genetic variants. Thus, the potential for utility of genetic characterization of individual patients as a predictor of anti-hypertensive response has yet to be realized.

1. There has been considerable debate whether responses mediated via beta1- and beta2-adrenoceptors (beta1ARs and beta2ARs) display the same degree of desensitization after prolonged or repeated exposure to agonists. 2. Examples are provided for selective desensitization of functional responses and loss of binding sites for beta1ARs. Equally, examples are given of selective desensitization and down-regulation involving beta2ARs. 3. This review examines whether receptor subtype-selective desensitization of betaAR-mediated responses can occur and whether even within the same subtype, there may be tissue-selective desensitization. Possible reasons why apparent selectivity of desensitization of functional responses may occur are considered and are divided into methodological and non-methodological factors. 4. Methodological factors discussed are: the concentration of agonist used for inducing desensitization and the washout times before construction of the post-incubation concentration-response curve (CRC), the need for correction of CRCs from time-matched controls, and the methods adopted for plotting CRCs. 5. Four non-methodological factors are considered. Firstly, the roles of different receptor reserves for the responses of each tissue can have an important effect on whether desensitization is apparent; a large reserve will make desensitization less likely to be apparent. Secondly, there is more than one site at which desensitization occurs; receptors are uncoupled from adenylyl cyclase activation, there is an additional site at the level of stimulation of cyclic AMP-dependent protein kinase and betaARs may ultimately be down-regulated. These processes may differ depending on the tissue and conditions and this may influence whether differential desensitization occurs between tissues. Thirdly, the apparent degree of desensitization after washout of an agonist can depend upon the rate of resensitization. Experiments to overcome this problem are described which demonstrate betaAR desensitization in the continued presence of agonist. Finally, the role of up-regulation of PDE in desensitization is discussed.