Enhanced secretion of tumour necrosis factor in patients with myocardial infarction.

OBJECTIVES: Recent evidence suggests that leukocyte infiltration of myocardial tissue may extend the area of necrosis during the acute phase of myocardial infarction. Since the activation of leukocytes depends on the action of cytokines, mainly tumour necrosis factor (TNF), we evaluated TNF secretion during myocardial infarction. METHODS: The study included 12 patients with acute myocardial infarction as diagnosed on the basis of enzymatic and ECG criteria. Patients were admitted within 3 hours from onset of chest pain. Serum levels of TNF were measured by immunoradiometric assay on venous blood samples collected at time 0, and at 6, 12 and 18 hours and 1, 2, 4 and 7 days following myocardial infarction. Plasma levels of atrial natriuretic peptide-alpha (ANP) were also measured on the same samples. RESULTS: Mean TNF levels significantly increased during the myocardial infarction, with a peak within the first 24 hours (p < 0.01). They remained significantly elevated until day 4 (p < 0.05). The rise in TNF was positively correlated with creatinine kinase levels. ANP was also significantly increased with a delayed peak after that of TNF (p < 0.01). CONCLUSION: Even though limited to a small number of cases, this study shows that acute myocardial infarction is associated with increased TNF secretion. Because of its capacity of stimulating leukocyte infiltration in myocardial tissue, the increased levels of TNF might potentially have a negative prognostic significance.

Decrease in cholesterol levels during the immunotherapy of cancer with interleukin-2.

IL-2, in addition to its immunomodulating and antitumour properties, induces important systemic actions, including cardiovascular, neuroendocrine and metabolic effects. The present study was carried out to evaluate IL-2 effects on cholesterol metabolism. The study included 14 advanced cancer patients (renal carcinoma: ten; colon carcinoma: four), who received IL-2 subcutaneously at a dose of 1.8 x 10(6) IU ml-2 twice daily for 5 days/week for 6 weeks. Venous blood samples were collected 7 days before, on days 0, 3, 7, 14, 21, 42 of IL-2 therapy, and on days 14 and 28 of the rest-period. IL-2 induced a rapid and evident decrease in cholesterol levels, with a normalisation of its concentrations within 7 days in 10/10 hypercholesterolemic patients. The lowest mean levels of cholesterol were reached within the first 2 weeks; after that they still slowly increased. LDL-/HDL-cholesterol ratio was significantly reduced by IL-2 therapy. Cholesterol fall was associated with a marked increase in conjugated biliary acid levels. Finally, triglyceride values increased during IL-2 therapy, but not in a significant manner. These results, by showing that IL-2 exerts an evident and very rapid cholesterol-lowering activity, would represent a further demonstration of the physiological importance of cytokines in the control of cholesterol metabolism.

[Cardioangioimmunology: the immune implications in the principle cardiovascular pathologies]. / Cardio-angio-immunologia: implicazioni immunitarie nelle principali patologie cardiovascolari.

At present, it is known that the immune system acts through the release of protein factors, so-called cytokines. In addition to their immunomodulating and endocrinometabolic effects, cytokines have appeared to be able to have an influence on the cardiovascular system by inducing important haemodynamic changes. Cytokines cause hypotension, particularly IL-2 and TNF, due at least in part to a production of nitric oxide by endothelial cells. Cytokines, such as IL-1, IL-6 and TNF, stimulate myocardial infiltration by activating leukocytes and inducing the release of cytotoxic factors during myocardial infarction; that would extend the area of necrosis. Finally, cytokines would be involved in the pathogenesis of the atherosclerosis, and cholesterol metabolism itself would be under a cytokine control. On these bases, it is possible to suggest in the near future the elaboration of new therapeutic strategies and prognostic indications, according to the bioimmunological response of patients with cardiovascular diseases.

Melatonin response to atrial natriuretic peptide administration in healthy volunteers.

Recent observations have demonstrated that the pineal hormone melatonin (MLT) plays a role in the neuroendocrine control of the cardiovascular system. On the other hand, it has been observed that the cardiac hormone alpha-atrial natriuretic peptide (ANP) may regulate the neuroendocrine functions. The present study was carried out to investigate the possible relationship between cardiac and pineal endocrine functions. Six healthy volunteers were treated on two different occasions with placebo or ANP at a dose of 0.1 mg i.v. as a bolus. An increase of greater than 100% in MLT serum levels was seen in 2/6 subjects. These preliminary results would suggest that ANP may play a role in the regulation of MLT secretion. Further studies will be needed to define better the cardiac-pineal interactions.