The aim of this review is to summarize the current concepts concerning the active role of the endothelium in the pathogenesis of atherosclerosis. Activated endothelium may promote the adhesion of monocytes and their transmigration into the intima. The coordinated expression of adhesion molecules of the selectin, integrin or immunoglobulin superfamily on the surface of endothelial cells and of monocytes modulates these events. The role of lipoproteins and their oxidative derivatives as well as that of selected cytokines and platelet activated factor in initiating changes on the endothelial cell surface has been investigated: these events are associated with an increased endothelial permeability to lipids and lipoproteins with their accumulation in the subendothelium. Once migrated into the intima, monocytes undergo morphological and functional modifications leading to the generation of a polypeptide mediator network which is instrumental in the migration, differentiation and proliferation of smooth muscle cells. Mediators produced by macrophages infiltrating the atherosclerotic plaque and by the endothelium may render the surface of the endothelial cells thrombogenic thus favoring thrombotic occlusion. In conclusion, the most recent studies suggest that the endothelium plays an active role in the pathogenesis of atherosclerosis.

Arteriosclerosis↗

PubMedDate not supplied

Immune effects of preoperative immunotherapy with high-dose subcutaneous interleukin-2 versus neuroimmunotherapy with low-dose interleukin-2 plus the neurohormone melatonin in gastrointestinal tract tumor patients.

Surgery-induced immunosuppression could influence tumor/host interactions in surgically treated cancer patients. Previous studies have shown that high-dose IL-2 preoperative therapy may neutralize surgery-induced lymphocytopenia. Moreover, experimental studies have demonstrated that the immunomodulating neurohormone melatonin (MLT) may amplify IL-2 activity and reduce its dose required to activate the immune system. On this basis, we have compared the immune effects of presurgical therapy with high-dose IL-2 with respect to those obtained with preoperative neuroimmunotherapy consisting of low-dose IL-2 plus MLT. The study included 30 patients with gastrointestinal tract tumors, who were randomized to undergo surgery alone, or surgery plus a preoperative biotherapy with high-dose IL-2 (18 million IU/day subcutaneously for 3 days) or low-dose IL-2 (6 million IU/day subcutaneously for 5 days) plus MLT (40 mg/day orally). Patients underwent surgery within 36 hours from IL-2 interruption. Both IL-2 plus MLT were able to prevent surgery-induced lymphocytopenia. However, mean number of lymphocytes, T lymphocytes and T helper lymphocytes observed on day 1 of postoperative period was significantly higher in patients treated with IL-2 plus MLT than in those receiving IL-2 alone. Moreover, toxicity was less in patients treated with IL-2 and MLT. This biological study shows that both immunotherapy with high-dose IL-2 or neuroimmunotherapy with low-dose IL-2 plus MLT preoperatively are tolerated biotherapies, capable of neutralizing surgery-induced lymphocytopenia in cancer patients. Moreover, the study would suggest that the neuroimmunotherapy may induce a more rapid effect on postoperative immune changes with respect to IL-2 alone.

Adult↗