Abstract
High levels of inflammation play an important role in chronic heart failure (CHF). Patients with CHF have elevated levels of pro-inflammatory cytokines circulating systemically, mainly TNF and IL-6. However, there are almost no studies that relate these levels to the functional status of patients in CHF, much less to their CMV serostatus. In this study, patients with CHF (n=40; age=54.9 ± 6.3; New York Heart Association functional classification (NYHA, I-III) and healthy controls (n=40; age=53.5 ± 7.1) were analyzed. The serum concentrations of nine pro- and anti-inflammatory cytokines were measured by Luminex® xMap Technology and the basal level of mRNA expression of some immune molecules was quantified by TaqMan™ Array in CD4+ T-lymphocytes. The concentration of these cytokines in culture supernatants in response to anti-CD3 and LPS was also measured. The percentage of CD28null T-cells was determined, as well as the antibody titer against CMV. We found a higher concentration of all cytokines studied in CHF serum compared to healthy controls, as well as a direct correlation between functional status in CHF patients and levels of inflammatory cytokines. Moreover, the highest cytokine concentrations were found in patients with higher concentrations of lymphocytes lacking CD28 molecule. The cytokine production was much higher in CMV+ patients, and the production of these cytokines was found mainly in the T-lymphocytes of CMV+ patients in response to anti-CD3. Anti-CMV antibody levels were positively correlated with cytokine levels. The baseline expression of specific mRNA of the main molecules involved in the Th1 response, as well as molecules related to the CD4+CD28 null subset was higher in CMV+ patients. The cytokine concentrations are higher in CHF CMV+ patients and these concentrations are related to the production of antibodies against CMV. These high levels of cytokines are also associated with the more differentiated CD28null lymphocyte populations. All this, together with the dynamics of the pathology itself, makes CMV+ patients present a worse functional status and possibly a worse evolution of the pathology.
Highlights
The process known as immunosenescence may affect both the elderly and individuals of all ages with chronic inflammatory or infectious diseases
Characteristics of Studied Groups Related to CMV-Serostatus and Cytokine Levels In Table 1 we can see the characteristics of the two studied groups, chronic heart failure (CHF) patients and healthy control group (HC)
When we made statistical comparisons with the analysis of variance (ANOVA) test, we found significantly higher levels in total white blood cells (WBCs), monocytes, and neutrophils and significantly decreased levels in lymphocytes (Table 1)
Summary
The process known as immunosenescence may affect both the elderly and individuals of all ages with chronic inflammatory or infectious diseases. The aging of the immune system, mainly adaptive, has been associated with the presence of chronic and persistent antigens, as well as a low-level inflammatory state, maintained for a considerable period of time. All these processes lead to a dysregulation of the immune system, compromising immune responses, producing an increase in the frequency of highly differentiated T-lymphocytes, mainly with the loss of the CD28 molecule [2, 3]. The differentiation of T-lymphocytes and the increase in the concentration of proinflammatory cytokines in physiological aging, and in certain chronic diseases, are events that occur at the same time Because of this it is not at all clear what produces what. Differentiated Tlymphocytes are related to the production of inflammatory cytokines, while a high concentration of circulating cytokines has been related to the differentiation of T-lymphocytes
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