These results indicate that patients with Buerger’s disease have an altered production of several cytokines in response to different stimuli. The disturbances Selleckchem Galunisertib in immune cell reactivity could be a reason for the persistent immune inflammation in TAO, and may confirm the role of immune dysregulation in TAO disease.
It is essential to emphasize that the inflammatory response is closely related to tabagism, as the plasma cytokines of TAO former smoker patients were similar to the controls. We did not find any studies concerning plasma cytokines in TAO patients. So far, we have found only one report that examines cytokines in patients with TAO [17]. In this ex-vivo study, the authors observed abnormal production of IL-6, IL-12 and IL-10, increased apoptosis and increased levels of circulating immune complexes, which may explain the persistence of TAO immune inflammation. Vascular endothelial growth factor (VEGF) strongly promotes angiogenesis, and monocyte colony-stimulating factor (M-CSF) regulates the differentiation, proliferation and survival of monocytes selleck chemicals in TAO [18]. The data indicate that endothelial cells in
TAO can be activated in TAO and that vascular lesions are associated with TNF-α secretion by tissue-infiltrating inflammatory cells, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and E-selectin expression on endothelial cells and leucocyte adhesion via their ligands. The preferential expression of inducible adhesion molecules in microvessels and mononuclear inflammatory cells suggests that this is due probably to inflammation contributing to the persistence of the inflammatory process in TAO [19]. Although the cause of TAO disease remains unknown, a strong association with tobacco use has been established [3,20]. Use of or exposure to tobacco plays a central role in the initiation and progression of the disease. By using an antigen-sensitive thymidine-incorporation assay, Adar et al. [21] showed that patients with TAO have an increased
HSP90 cellular sensitivity to types I and III collagen compared to patients with arteriosclerosis obliterans or healthy males. De Moerloose et al. [22] found a marked decrease in the frequency of human leucocyte antigen (HLA)-B12 in patients with Buerger’s disease (2·2% versus 28% in controls). Similarly to other autoimmune diseases, TAO may have a genetic predisposition without a direct ‘causative’ gene mutation. Most investigators believe that TAO is an immune-mediated endarteritis. Immunocytochemical studies have demonstrated a linear deposition of immunoglobulins and complement factors along the elastic lamina [20,23]. Patients with Buerger’s disease present a statistically significantly higher frequency of HLA-DR4 and a significantly lower frequency of the HLA-DRW6 antigen.