Interleukin-1α As a Factor in Occlusive Vascular Disease

Abstract

The purpose of this study was to examine the recognized ability of interleukin-1 alpha (IL-1 alpha) to alter the functional properties of endothelial cells and to induce replication of smooth muscle and fibroblasts. Such changes could potentially link IL-1 alpha pathogenetically to the myointimal proliferation of vascular sclerosis. Using a peroxidase-immunoperoxidase immunohistochemical method, saphenous veins and internal mammary arteries were examined for the presence of IL-1 alpha before their implantation as aortocoronary bypass grafts. Occluded saphenous vein grafts requiring replacement because of recurrent angina pectoris also were similarly examined. Interleukin-1 alpha, deposited as a scarlet immunoprecipitate, was seen on the luminal surface, in the subintima, and on the spindle cells and infiltrating macrophages in the media of 13 phlebosclerotic veins before surgical insertion. The remaining 30 unchanged veins did not contain IL-1 alpha. Similarly, IL-1 alpha was not identified in any of the 43 sampled internal mammary arteries that were all considered structurally intact. All the 55 bypass grafts, which were examined by biopsy during revascularization and demonstrated diverse histopathologic abnormalities consisting of reduced luminal patency, myointimal proliferation, mononuclear cell infiltration, mural collagenization, and luminal-mural hemorrhage, also contained widely distributed IL-1 alpha. The observation that IL-1 alpha was absent in all of the internal mammary arteries concomitant with maintenance of normal microanatomic structure may help explain, in part, their recognized resistance to reduction in luminal patency and their improved clinical survival when used as coronary artery bypass grafts. Alternatively, the consistent presence of IL-1 alpha in all vessels with sclerotic histopathologic changes suggests that this cytokine may be an important in situ indicator of and a potential participant in vascular injury. Interleukin-1 alpha may be a pathogenetic factor in the complex processes leading to vascular occlusion.

Platelets as Immune Cells

“…[13][14][15]111,119 Moreover the strong proinflammatory mediator IL-1 is secreted by platelets and has an impact on atherosclerosis that is mediated at least by inducing alterations of the adhesive and chemotactic properties of endothelial cells. 130,137,[183][184][185] The glycoproteins GPIIb/IIIa and GPIb participate in platelet adhesion to the endothelium of atherosclerosis-prone mice that have not yet developed plaques and are involved in the deposition of chemokines from platelet-derived microparticles. 15,186 As underlying mechanisms, the involvement of GPIb may encompass binding to von Willebrand factor to support platelet adhesion or to leukocyte Mac-1 to support platelet/leukocyte aggregates.…”

Proinflammatory Cytokines in Heart Disease

“…This expression was associated with an increase in platelet-derived growth factor B chain synthesis in lipid-filled macrophages (foam cells) that had invaded the atheromatous lesions [25]. Using immunohistochemical staining, each of 55 sclerotic vein coronary artery bypass grafts revealed the presence of IL-1·, whereas nonoccluded internal mammary artery grafts did not [26]. The affected vessels also showed myointimal proliferation, reduced luminal patency and macrophage infiltration.…”

“…Several laboratories have demonstrated biologically active membrane-bound IL-1· [36,37], and immunohistochemical staining in diseased blood vessels also reveals the presence of IL-1· [26]. Human monocytes which have been fixed after lipopolysaccharide activation express IL-1· on their surface, and when incubated with cultured human endothelial cells, induced IL-8 production [38].…”

Endogenous interleukin-1α promotes a proliferative and proinflammatory phenotype in human vascular smooth muscle cells

“…The functions of endogenous VSMC-derived IL-1␣ in this context are unknown, but we have hypothesized that it may play an autocrine role in promoting VSMC proliferation, based on in vitro and in vivo lines of evidence. For example, in coronary bypass patients, IL-1␣ was found in spindle-shaped cells within saphenous vein grafts that had become stenotic but not in those that remained patent (5). Similarly, IL-1␣ mRNA was found in medial smooth muscle cells (SMC) within arterial lesions of hypercholesterolemic monkeys but not in normal arteries (21).…”