The Pro-resolution pathway is altered in Chronic Heart Failure: implications for adaptive immunity dysregulation

Chronic Heart Failure (CHF) is a syndrome affecting humans with a relevant immune component which contributes to the severity of the condition. Inflammation in CHF is characterized by an increased plasma level of pro-inflammatory cytokines which are the signal of the onset of acute inflammation that in absence of resolution might become chronic. Resolution of inflammation is a finely regulated process mediated by specialized pro-resolving lipid mediators (SPMs) including arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) derived molecules. In this work it has been shown that (DHA)-derived, also called D-series resolvins (RvDs), resolvin D1 (RvD1) and resolvin D2 (RvD2), are not able to modulate T cells immune responses in CHF patients and for this reason they could be involved in the failure of the resolution of chronic inflammation in this syndrome. Previously work has shown that RvD1 and RvD2 were able to modulate the immune activity of T lymphocytes, responsible for the adaptive immune response, in healthy humans. In this study we sought to investigate whether or not RvD1 and RvD2 are able to modulate the immune activity of T cells in CHF patients. ELISA test showed that plasma levels of RvD1 were greatly reduced in CHF patients compared with those of the healthy controls. In addition, both RvD1 and RvD2 were not able to modulate T cells immune responses in CHF patients. These results suggested that there might be a defective signaling in the pro-resolving pathway of RvDs in CHF. qRT-PCR reported a reduction of the expression in both key enzyme 15-lipoxygenase (15-LOX), involved in RvD1 and RvD2 biosynthesis, and RvD1 receptor GPR32 compared with controls, and western blotting analysis confirmed this reduction. These findings indicate that the failure of CHF patients to respond to the pro-resolving actions of RvDs is caused by defects in both biosynthetic and expression pathway of RvD1, and that this may participate in the progression of chronic inflammation. The pro-resolution pathway might be a potential candidate to design better treatments for CHF with the aim of reducing chronic inflammation.