ABSTRACT
BACKGROUND: Evidence shows that proinflammatory cytokines are important determinants of assessment of severity and prognosis of chronic heart failure (CHF). AIMS: We investigated whether peripheral expression of the proinflammmatory factors, TNF-α and IL-6 can predict variable of clinical assessment of patients with CHF. METHODS: In this report, we used real-time PCR assay to compare relative gene expression of TNFα and IL-6 in PBMC from CHF patients with various heart diseases (n = 42, EF < 45%, NYHA I to IV) and matched healthy control subjects (n = 42).We also determined the TNFα and IL-6 concentrations of cell culture supernatant of PBMCs with ELISA. RESULTS: There was a significant negative correlation between gene expression of TNFα and LVEF(r = 0.4, p < 0.05). Patients with CHF had increased gene expression of TNFα and IL-6 in PBMCs (p < 0.05). They also had elevated the supernatant levels of these cytokines in cultured PBMCs (p < 0.001). Levels of TNFα and IL-6 were increased in ischemic heart disease compared to non-ischemic heart disease. There was a positive correlation between TNFα and IL-6 levels in CHF patients and severity of CHF in patients. Levels of these cytokines were higher in patients with NYHA III-IV than in NYHA I-II and normal subjects. CONCLUSIONS: Results of this study indicate that peripheral expression of proinflammatory cytokines, TNF-α and IL-6, is important indicators of severity and prognosis in patients with chronic heart disease.
Subject(s)
Heart Failure/blood , Interleukin-6/genetics , Leukocytes, Mononuclear/metabolism , Tumor Necrosis Factor-alpha/genetics , Chronic Disease , Female , Heart Failure/mortality , Heart Failure/pathology , Humans , Male , Middle Aged , PrognosisABSTRACT
BACKGROUND: Distinct subsets of T cells play crucial regulatory roles in inflammatory processes of chronic heart failure (CHF). Retinoic acid receptor-related orphan receptor-γt (Ror-γt) and Forkhead box P3 (Foxp3) have been defined as the "master regulators" of Th17 cells and Treg cells, respectively. At the same time, anti-inflammatory cytokines such as IL-10 may neutralize inflammation in CHF. The current study was designed to compare FOXP3, RORγt and IL-10 protein expression in the blood and IL-10 in supernatant PBMCs in CHF patients versus normal subjects. PATIENTS AND METHODS: Our study population consisted of 42 patients with CHF in four different function classes and 42 healthy subjects who served as controls. RNA extraction and cDNA synthesis was performed and mRNA expression for genes FOXP3, RORγt, IL-10 was determined by RT-PCR. The amount of IL-10 protein in supernatant of PBMCs was measured by ELISA technique. RESULTS: There was no significant difference in FOXP3, RORγt, IL-10 protein expression and supernatant PBMCs IL-10 in CHF patients as compared to control. The level of Foxp3 was significantly lower in CHF patients with ischemic vs non-ischemic cause (p = 0.04). DISCUSSION: Although inflammation plays a central role in the pathophysiology of CHF, the roles of FOXp3, RORγt, and IL-10 remain to be determined (Tab. 3, Ref. 33).
Subject(s)
Forkhead Transcription Factors/immunology , Heart Failure/immunology , Interleukin-10/immunology , Nuclear Receptor Subfamily 1, Group F, Member 3/immunology , Adult , Aged , Case-Control Studies , Chronic Disease , Female , Forkhead Transcription Factors/genetics , Heart Failure/genetics , Humans , Inflammation , Interleukin-10/genetics , Leukocytes, Mononuclear/immunology , Male , Middle Aged , Nuclear Receptor Subfamily 1, Group F, Member 3/genetics , RNA, Messenger/metabolism , T-Lymphocytes, Regulatory/immunology , Th17 Cells/immunologyABSTRACT
BACKGROUND: Proinflammatory cytokines have been known to play a considerable part in the pathomechanisms of chronic heart failure (CHF). Given the importance of proinflammatory cytokines in the context of the failing heart, we assessed whether the polymorphisms of interleukin (IL)-1 gene cluster, including IL-1α, IL-1ß, and IL-1 receptor antagonist (IL-1RA) and IL-1R gene are predictors of CHF due to ischemic heart disease. METHODS: Forty- three patients with ischemic heart failure were recruited in this study as patients group and compared with 140 healthy unrelated control subjects. Using polymerase chain reaction with sequence-specific primers method, the allele and genotype frequency of 5 single nucleotide polymorphisms (SNPs) within the IL-1α (-889), IL-1ß (-511, +3962), IL-1R (psti 1970), and IL-1RA (mspa1 11100) genes were determined. RESULTS: The frequency of the IL-1ß -511/C allele was significantly higher in the patient group compared to that in the control group (p = 0.031). The IL-1ß (-511) C/C genotype was significantly overrepresented in patients compared to controls (p = 0.022). CONCLUSIONS: Particular allele and genotype in IL-1ß gene were overrepresented in patients with ischemic heart failure, possibly affecting the individual susceptibility to this disease (Tab. 1, Ref. 27).
