Original article
Increased serum levels of interleukin-1β in the systemic circulation of patients with essential hypertension: Additional risk factor for atherogenesis in hypertensive patients?

https://doi.org/10.1016/S0022-2143(97)90178-5Get rights and content

Abstract

The dysfunction of the immune system has been implicated in the cause of essential hypertension (EH). On the other hand, interleukin-1β (IL-1β) has strongly been involved in the pathogenesis of atheromatosis, whereas our preliminary experiments in serum samples from hypertensive patients before any drug therapy have shown the presence of high concentrations of IL-1β and the absence of interleukin-2 (IL-2). The aim of this study was first to confirm our preliminary findings and second to investigate the possible interrelation(s) among the parameters studied, particularly between the immunologic markers and the blood pressure or the lipid parameters, because so far there are no data regarding the possible participation of IL-1β in the cascade phenomena presented during the process of EH such as atherogenesis. Serum samples from 28 consecutive unselected patients with EH before any drug administration or after discontinuation of the antihypertensive therapy for at least 4 weeks, 31 normotensive patients with familial hypercholesterolemia (FH, disease control group), and 35 healthy individuals in a control group matched for age and sex were investigated for the presence of IL-1β (commercial enzyme immunoassay), soluble IL-2 receptors (sIL-2Rs, sandwich enzyme-linked immunosorbent assay set up in our laboratory), and some of the acute phase proteins by nephelometry. In addition, total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoproteins A1 and B, and lipoprotein (a) were determined by standard methods. The data were analyzed by unpaired t test, Mann Whitney-U, chi-squared analysis after Yate's correction, analysis of variance, or Kruskal-Wallis where applicable. Correlation coefficient was calculated by simple regression analysis (r) or nonparametric Spearman correlation coefficient (rs). We found that (1) none of the patients had increased concentrations of sIL-2Rs, and (2) the IL-1β levels significantly differed in the three groups (p = 0.0001). In more detail, the concentrations of IL-1β were significantly higher in patients with EH compared with those in patients with FH (p < 0.0005) and the healthy control group (p = 0.0001). By contrast, the IL-1β concentrations did not differ between patients with FH and the healthy control group. (3) Sixteen (57.1%) patients with EH and only 6 (19.4%) patients with FH (p < 0.01) had increased levels of IL-1β, and (4) the IL-1β was not correlated with the acute phase reactants or the lipid parameters in the groups studied. However, the group of patients with EH and increased IL-1β levels had significantly higher mean concentrations of triglycerides (p < 0.05) and significantly lower mean concentrations of high-density lipoprotein cholesterol (p < 0.05) than those who had IL-1β levels lower than the cutoff point. (5) The IL-1β concentrations were positively though slightly correlated with the mean blood pressure only in the group of patients with EH (r = 0.38, p < 0.05). This study demonstrated the presence of high concentrations of IL-1β and the absence of indicators of cellular immune activation in the systemic circulation of patients with EH, suggesting that this cytokine may be involved in the pathogenesis of EH. In addition, this study showed that the high levels of IL-1β were associated with lipid indicators of atheromatosis only in the group of patients with EH. More studies are required in an attempt to address whether IL-1β could have a pathogenetic importance in EH. Taking into account these findings, however, it can be suggested that the presence of high IL-1β levels may be an additional and perhaps independent risk factor for atheromatosis in patients with EH.

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