A. Auteri

Extracorporeal photochemotherapy restores Th1/Th2 imbalance in patients with early stage cutaneous T‐cell lymphoma

Extracorporeal photochemotherapy (ECP) has been shown to be a potent activator of peripheral blood macrophages because it causes a marked release of macrophage‐dependent proinflammatory cytokines, and it is therefore currently considered to be a safe and non‐toxic immunomodulatory treatment. On this basis we studied the function of peripheral blood mononuclear cells (PBMC) in eight patients with early stage (Ib) cutaneous T‐cell lymphoma (CTCL), before and 1 year after ECP, together with their clinical and histological responses. In particular we evaluated in vitro phytohaemagglutinin (PHA)‐stimulated proliferation and production of interleukin‐4 (IL‐4) and interferon‐&ggr; (IFN‐&ggr;) as well as lipopolysaccharide (LPS)‐induced production of IL‐12. Before treatment we observed that PBMC of patients produced significantly higher levels of IL‐4 and lower levels of IFN‐&ggr; and IL‐12 than those of healthy control subjects. After 1 year of ECP, IL‐4, IFN‐&ggr; and IL‐12 production no longer differed from that of control subjects. Moreover, we observed a good clinical result matched by histological response. Our data confirm that early‐ stage CTCL patients show a predominantly type‐2 immune response that might be responsible for several immunological abnormalities found in this disease. We have demonstrated that ECP reverses the T‐helper type 1/T‐helper type 2 (Th1/Th2) imbalance and may therefore be considered an efficient biological response modifier.

Time‐dependent effect of statins on platelet function in hypercholesterolaemia

Background Reduction of platelet activity induced by statins has been described as a positive effect exerted by such molecules on vascular thrombotic events. However, the relations among cholesterol (LDL‐C) reduction, the timing of the antiplatelet effect, the involved mechanisms and the doses of each statin able to reduce platelet function are not actually well known. The aim of our study was to evaluate the impact of simvastatin (20 mg day−1), atorvastatin (10 mg day−1), fluvastatin (40 mg day−1) and pravastatin (40 mg day−1) on platelet function in hypercholesterolaemic subjects with relation to (LDL‐C), oxidized‐LDL (ox‐LDL) and antiport mechanism modifications.

Common variable immunodeficiency: a review.

Abstract.Common variable immunodeficiency (CVID) is the commonest symptomatic primary antibody deficiency syndrome. The predominant manifestation is hypogammaglobulinemia. CVID is characterized by recurrent bacterial infections, especially of the upper and lower respiratory airways, and is also associated with an increased incidence of autoimmune and neoplastic disorders. Most patients are diagnosed as adults and delay in the recognition of the disease is common. Several T and B cell defects have been described, although the underlying cause is still unknown.

Platelet hyperactivity after statin treatment discontinuation

Hydroxymethyl-glutaryl-CoA-reductase inhibitors (statins) reduce cardiovascular events by cholesterol lowering as well as by non-lipid related actions. Among them, the modulation of platelet activity could play a relevant role in vascular protection. Furthermore withdrawal of statins has been associated with increased cardiovascular event rate. The aim of our study was to evaluate platelet activity after cerivastatin discontinuation in eighteen subjects that did not accept other drugs and in sixteen subjects continuing treatment with simvastatin. Fourteen subjects at the end of the discontinuation period decided to receive other drugs (simvastatin) and they were evaluted six weeks later. We measured complete lipid profile by the chromogenic method (LDL-C was calculated); oxidized-LDL (ox-LDL; ELISA), platelet P-selectin (P-sel) expression (flow cytometry detection), platelet aggregation (% change of transmitted light), intracellular citrullin production (iCit; HPLC) as an indicator of intracellular NO synthase activity at baseline and 7, 14, 28, 60 days after statin discontinuation. P-sel expression and platelet aggregation were increased at 14 days (p < 0.001 and p < 0.05) in association with raised ox-LDL (r = 0.30, p < 0.05) and decreased iCit (r = 0.53, p < 0.01). Increased LDL-C was related to P-sel and platelet aggregation at 28 days (r = 0.30, p < 0.05). Subjects continuing statin treatment had no significant changes of P-sel at 28 (p = 0.221) and 60 days (p = 0.238). Subjects treated with simvastatin after 60 days of diet showed a significant reduction of P-sel and platelet aggregation after six weeks of treatment (p < 0.01). Our data suggest a platelet hyperactivation state in the second week after statin discontinuation which is partially related to raised LDL-C. Such a finding could participate in the increased cardiovascular event rate after statin discontinuation.

Atorvastatin reduces platelet-oxidized-LDL receptor expression in hypercholesterolaemic patients

Background  Oxidized‐LDL (ox‐LDL) are proatherogenic and platelet‐activating molecules. Atorvastatin reduces platelet activity before cholesterol‐lowering action. CD36 and lectin‐like oxidized‐LDL receptor‐1 (LOX‐1) are specific ox‐LDL receptors expressed also in platelets. This study was planned to address whether the possible rapid effect of atorvastatin on platelets could be related to modulation of ox‐LDL receptors.

Erratum to “Pro/Anti-Inflammatory Cytokine Imbalance in Postischemic Left Ventricular Remodeling”

The authors would like to inform the correct names for the present paper as stated above.

Takayasu's arteritis: a review of the literature.

Takayasus arteritis is a rare, idiopathic, chronic inflammatory disease with cell-mediated inflammation, involving mainly the aorta and its major branches. It leads to stenosis, occlusion or aneurysmal degeneration of large arteries. The clinical presentation is characterised by an acute phase with constitutional symptoms, followed, months or years later, by a chronic phase in which symptoms relate to fibrosis or occlusion of vessels. Angiography is the gold standard for diagnosis and for topographical classification and it correlates with symptoms and prognosis. Here we focus on the pathophysiology, clinical and angiographical classification, diagnostic assessment and therapeutic approach of Takayasus arteritis.

Effects of carvedilol on left ventricular remodeling and systolic function in elderly patients with heart failure

Recent studies have shown that carvedilol therapy in patients with heart failure improves clinical outcome and survival, however, the effects of such treatment on left cardiac morphology and function in elderly patients with severe heart failure has not been widely studied.

Extracorporeal photopheresis affects co‐stimulatory molecule expression and interleukin‐10 production by dendritic cells in graft‐versus‐host disease patients

Graft‐versus‐host disease (GVHD) is a major complication of allogeneic bone marrow transplantation. Extracorporeal photochemotherapy (ECP) has been introduced as an alternative treatment for GVHD refractory to conventional immunosuppressive treatment, although its mechanism of action is not yet clear. We investigated, in seven GVHD patients, the effects of ECP on dendritic cell maturation and cytokine production in an in vitro model that could mimic the potential in vivo effect of reinfusion of ECP‐treated peripheral blood mononuclear cells. The model was based on co‐culture of ECP‐treated lymphocytes with monocyte‐derived dendritic cells (DCs) of the same patient. We found that the co‐culture of ECP‐treated lymphocytes with immature DCs reduced CD54, CD40 and CD86 mean fluorescence intensity (MFI) significantly after lipopolysaccharide (LPS) stimulation, without affecting human leucocyte antigen D‐related and CD80 MFI. In the same co‐culture model, DCs produced increased amounts of interleukin (IL)‐10 when co‐cultured with ECP‐treated lymphocytes and stimulated with LPS, while IL‐12 and tumour necrosis factor‐α production were not affected. These results suggest that reinfusion of large numbers of autologous apoptotic lymphocytes is significant for the therapeutic outcome of ECP through down‐regulation of co‐stimulatory molecules on DCs, inducing non‐fully mature DCs with a low signal 2 and up‐regulation of IL‐10, which is an immunosuppressive cytokine.

Pro-inflammatory/anti-inflammatory cytokine imbalance in acute coronary syndromes

The aim of this study was to evaluate the presence of an imbalance between proinflammatory and anti-inflammatory mediators in patients affected by acute coronary syndromes (ACS). We considered two groups of 26 and 28 patients with acute myocardial infarction (AMI) and unstable angina (UA) respectively, compared with a group of 30 patients with stable angina and 30 healthy volunteers. We evaluated the production in cultured and stimulated lymphomonocytes of interferon (IFN)γ and tumour necrosis factor (TNF)α, which are well known to possess proinflammatory effects, and of interleukin (IL)10, which has been shown to have a protective anti-inflammatory activity. We also assessed the clinical characteristics of groups and, particularly, we evaluated the circulating levels of C-reactive protein (hs-CRP). We found a significant increase of IFNγ and TNFα production (P<0.01) and a significant decrease of IL10 production (P<0.05) in cultures of lymphomonocytes taken from patients with AMI and UA compared with SA patients and controls. No significant changes where found between AMI and UA patients and SA patients and controls. Circulating levels of hs-CRP were significantly increased (P<0.01) in patients with ACS compared with the other control groups. Our data showed an increased production of proinflammatory mediators in ACS that may be detectable both in circulating blood and in cell cultures where it is possible to evaluate in a better way the functional state of cells; this finding was associated with a reduced production of the antiinflammatory cytokine IL10. In conclusion, a relevant imbalance is present in ACS and this fact could contribute to plaque instability and clinical manifestations.