The effect of-IL-6 on OX-LDL induced immunomodulation in atherosclerotic patients and healthy subjects

Abstract

Atherosclerosis, a progressive inflammatory disease, is marked by the expansion of atherosclerotic plaques within the injured arterial wall in response to various harmful insults contributing to the vessel wall damage. Among the latter transgressors, oxidized low-density lipoprotein (ox-LDL), and a whole range of associated cytokines predominantly IL-6 and IL17, pro-inflammatory T-helper 17 (Th17) cells signature cytokines, as well as TGF-β and IL10, anti-inflammatory CD4+CD25+FoxP3+ regulatory T (Treg) cells characteristic cytokines, have been all shown to be key mediators of atherogenesis. In our study we evaluated the modulation/alteration of the immune status concomitant with ox-LDL and IL-6 in atherosclerotic patients. Accordingly, we examined the effect of ox-LDL, IL-6 and the combination of both on the frequency of CD4+CD25+ Foxp3+ T cells, and relevant cytokines, mainly Treg signature cytokine IL-10 and Th17 signature cytokine IL-17, in patients with stable angina (SA) and subjects with normal coronary arteries (NCA). In order to accomplish our aim, isolated peripheral blood mononuclear cells (PBMCs) were treated with ox-LDL, IL6, and ox-LDL+ IL-6 followed by a 4 day incubation period. T-reg cells evaluation was accomplished via T regulatory staining and further quantification of the cytokine (IL-10 and IL-17) levels was assessed by employing the supernatant of cultured PBMCs through ELISA assays. Our results demonstrated no significant difference regarding T regulatory frequency, il-10 and IL-17 secretion levels among SA and NCA. However, within the same group IL10 and IL-17 secretion levels were significantly different among the diverse conditions of treatment; IL-10 levels were significantly decreased upon the addition of ox-LDL whereas IL17 levels were significantly increased upon addition of IL-6. SA and NCA displayed almost a similar pattern of susceptibility for antigenic oxLDL and IL-6 thus, it was the environment (ox-LDL, IL-6, ox-LDL+IL-6) surrounding the PBMCs which caused the variation in the cytokine levels (IL-10, IL-17) regardless of the PBMC source (SA or NCA).