Immunological Parameters, Including CXCL8 (IL-8) Characterize Cerebro- and Cardiovascular Events in Patients with Peripheral Artery Diseases

Abstract

The most commonly occurring atherosclerotic manifestations are peripheral artery diseases (PAD). Immune-mediated processes contribute to the development of atherosclerosis, and affect the diseases outcome. The aim of the present study was to assess various immune-competent cells, cytokines and chemokines in patients with PAD and to evaluate whether the base immunological values reflect the subsequent development of cardio/cerebrovascular symptoms. One hundred sixty patients with PAD were followed-up for 42 months. At the time of enrolment, we determined blood lymphocyte subpopulations, both T-helper (Th)1/Th2-type intracytoplasmic cytokines and soluble cytokines, chemokines. Intracellular cytokines were measured on phorbol-myristate-acetate- and ionomycine- stimulated cells. Lymphocyte subgroups were quantified by flow cytometry, soluble cytokines by ELISA and intracellular cytokine levels were measured by flow cytometry. The ankle-brachial index (ABI), indicator of atherosclerosis, was also evaluated. The clinical results were correlated with the immune-parameters to assess the input of immune-inflammatory events in the propagation of vascular manifestation. CD4(+) T-cell proportions in patients with PAD with cerebro- cardio-vascular manifestations were decreased, which further reduced in patients with fatal outcome. Of circulating chemokines, IL-8 (CXCL-8) was increased in patients with subsequent cerebro- cardio-vascular manifestations, compared to those without the symptoms, and further raised in patients with fatal outcome. The percentage of interferon (IFN)-gamma positive cells showed clear negative correlation with ABI. We conclude that altered peripheral lymphocyte subsets and cytokine/chemokine imbalance play important roles in the proinflammatory cascade and reflect disease severity in patients with PAD.