Activation of cytokines corroborate with development of inflammation and autoimmunity in thromboangiitis obliterans patients

Abstract

SummaryThromboangiitis obliterans (TAO) is a segmental inflammatory occlusive disorder that affects the arm and leg arteries of young smokers. The immune system seems to play a critical role in the aetiology of TAO; however, knowledge of the aspects involved in the progression of vascular tissue inflammation and, consequently, the evolution of this disease is still limited. This study was carried out to investigate the cytokine levels of tumour necrosis factor (TNF)-a, interleukin (IL)-1b, IL-4, IL-17 and IL-23 in the plasma of TAO patients presenting with acute clinical manifestations. The study included 20 TAO patients (n = 10 women; n = 10 men) aged 38-59 years under clinical follow-up, classified into two groups: (i) TAO former smokers (n = 11) and (ii) TAO active smokers (n = 9); the control groups included normal volunteer non-smokers (n = 10, active smokers (n = 10) and former smokers (n = 10). Patients' plasma samples were measured using the sandwich enzyme-linked immunosorbent assay. Statistical analyses were performed using the non-parametric Mann-Whitney U-test, with parameters significant at P < 0·05. The activities of all cytokines were different in groups of TAO patients when compared with normal controls, and decreased for control smokers. Increased levels of TNF-a, IL-1b, IL-4, IL-17 and IL-23 were significant in patients with TAO when compared to the controls (P < 0·005, all parameters). The results presented here indicate an increased production of cytokines in TAO, possibly contributing to the inflammatory response observed in the patients' vascular levels. In addition, the increased levels of IL-17 and IL-23 suggest that the disturbance of TAO is involved with mechanisms of autoimmunity. Thus, the discovery of IL-17 and its association with inflammation and autoimmune pathology has reshaped our viewpoint regarding the pathogenesis of TAO, which was based previously on the T helper type 1 (Th1)-Th2 paradigm.

Associations Between Elevated Plasma Total Homocysteine Level and Risk of Thromboangiitis Obliterans in a Chinese Population: A Matched Case-Control Study

“…In addition, smoking can directly cause interleukin-33einduced inflammatory cell infiltration into the blood vessel wall with consequent release of inflammatory mediators that damage vascular endothelial cells in turn leading to the formation of cellular inflammatory thrombus and the acute phase of TAO. 23,24 The only proven strategy to prevent the progression of TAO is the complete cessation of smoking or any other form of tobacco use. Surgical revascularization is usually not appropriate for patients with TAO because of the distal and diffuse involvement of the disease rendering it improbable to find an outflow tract for bypass surgery and endovascular therapy.…”

Buerger's disease: autoimmune disease involving multiple hypersensitivity types

“…Various antibodies in TAO have been reported, including anti-endothelial cell antibodies [5], anti-neutrophil cytoplasmic antibodies [6], anti-phospholipid antibodies [7], anti-cardiolipin antibodies [8], and agonistic auto-antibodies directly against the G-protein coupled receptor [9]. TAO is associated with elevated cytokine levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-4, IL-6, IL-17, and IL-23 [10,11]. TAO is also associated with an increased expression of vascular cell adhesion molecules, intracellular adhesion molecules, and E-selectin on the endothelial cells of the affected arteries [12].…”

Efficacy of bosentan in patients with refractory thromboangiitis obliterans (Buerger disease)

“…One of the key findings in the immunopathogenesis of this disease is the injury to vascular endothelium, resulting in activation of the inflammatory response. [4,20,21] Pathohistologically, TAO lesions are categorized into 3 phases, including acute, subacute, and chronic, according to the thrombus pattern and the nature of the inflammatory cells. [20] Signs of endothelial activation and proliferation, and also the presence of immunocompetent cells, are only seen in acute-type lesions.…”

“…Immunoglobulin and complement deposition, and also CD4+ and CD8+ T lymphocytes, CD20+ B lymphocytes, and S100 positive dendritic cells are found alongside the lamina elastica interna, which become structurally altered, but are typically preserved. [4,20,21] An impaired endothelium-dependent vasorelaxation in the peripheral vasculature, even in the nondiseased limbs, has been observed in TAO. [5–7] Bosentan has been shown to improve endothelial function in patients with systemic sclerosis, [22] and, according to the results of the study of De Haro et al, [11,12] who measured it indirectly by means of BAFMD, also in TAO patients.…”