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Varani S.,University of Bologna | Rossini G.,University of Bologna | Mastroianni A.,Unit of Infectious Diseases | Tammik C.,Karolinska Institutet | And 4 more authors.
Journal of Clinical Virology | Year: 2012

Background: In vitro studies suggest that human cytomegalovirus modulates the functions of dendritic cells (DCs). However, there are limited data on DC homeostasis in CMV-infected patients. Objectives: The aim of this study was to characterize circulating DCs and plasma cytokine levels in immunocompetent patients with primary, symptomatic CMV infections. Study design: The study population consisted of 14 patients suffering of CMV mononucleosis and 14 healthy volunteers (11 CMV-seropositive and 3 CMV-seronegative subjects) included as controls. Peripheral blood mononuclear cells were isolated and used to characterize DCs and to quantify CMV in the blood. Plasma levels of pro-inflammatory and anti-inflammatory cytokines were also measured. Results: We observed that patients who were developing CMV mononucleosis presented lower myeloid and plasmacytoid DC counts in peripheral blood compared with healthy controls. We also noted elevated levels of inflammatory mediators, of which tumor necrosis factor-α (TNF-α)-which activates DCs and endothelial cells-was the highest. Notably, the decrease in blood DCs correlated with high TNF-α and IL-8 levels by a hyperbolic function. Conclusions: Our results suggest that increased levels of inflammatory factors facilitate alterations in DC homeostasis during primary CMV infection, which may contribute to viral-induced modulation of host immunity. © 2012 Elsevier B.V.

Fisicaro P.,Laboratory of Viral Immunopathology | Valdatta C.,Laboratory of Viral Immunopathology | Massari M.,Unit of Infectious Diseases | Loggi E.,University of Bologna | And 6 more authors.
Gastroenterology | Year: 2010

Background & Aims: The antiviral function of peripheral hepatitis B virus (HBV)-specific T cells can be increased in patients with chronic hepatitis B by blocking the interaction of programmed death (PD)-1 with its ligand PD-L1. However, no information is available about the effects of this blockade on intrahepatic lymphocytes. We studied T-cell exhaustion and the effects of PD-1/PD-L1 blockade on intrahepatic and circulating HBV-specific T cells in patients with chronic hepatitis B. Methods: A total of 42 patients with chronic HBV infection who underwent liver biopsy were studied. The ex vivo phenotype of peripheral and intrahepatic HBV-specific CD8+ T cells was assessed by flow cytometry with class I tetramers and antibodies to T-cell differentiation molecules. Functional recovery was evaluated by analyzing expansion and production of interferon (IFN)-γ and interleukin (IL)-2 after short-term incubation of T cells with HBV peptides in the presence of anti-PD-L1 or control antibodies. Results: Intrahepatic HBV-specific CD8+ cells expressed higher levels of PD-1 and lower levels of CD127 than their peripheral counterparts. Blockade of PD-1/PD-L1 interaction increased CD8+ cell proliferation and IFN-γ and IL-2 production by circulating intrahepatic lymphocytes, even though anti-PD-L1 had a stronger effect on intrahepatic compared with peripheral T cells. Conclusions: T-cell exhaustion by high antigen concentrations promotes HBV-specific T-cell dysfunction by affecting phenotype and function of peripheral and intrahepatic T cells. By restoring antiviral T-cell functions, not only in peripheral but also in intrahepatic lymphocytes, anti-PD-L1 might be a good therapeutic candidate for chronic HBV infection. © 2010 AGA Institute.

Kouroumichakis I.,Democritus University of Thrace | Papanas N.,Democritus University of Thrace | Proikaki S.,Democritus University of Thrace | Zarogoulidis P.,Unit of Infectious Diseases | Maltezos E.,Democritus University of Thrace
European Journal of Internal Medicine | Year: 2011

Severe sepsis is an infection-induced inflammatory syndrome that can lead to multi-organ dysfunction and continues to be a major cause of morbidity and mortality worldwide. Because numerous cascades are triggered during sepsis, selective blocking of inflammatory mediators may be insufficient to arrest this process, and recent therapeutic approaches have proven controversial. Statins are the most commonly prescribed agents for hypercholesterolaemia and dominate the area of cardiovascular risk reduction. Moreover, these drugs have a variety of actions that are independent of their lipid lowering effect. Such anti-inflammatory, antioxidant, immunomodulatory, and antiapoptotic features have been collectively referred to as pleiotropic effects. By virtue of their pleiotropic effects, statins have also emerged as potentially useful in various critical care areas such as bacteraemia, the early phases of sepsis and septic shock, as well as the management of serious infections. This review outlines current evidence on the use of statins for preventing and treating sepsis. © 2010 European Federation of Internal Medicine.

Madeddu G.,University of Sassari | Menzaghi B.,Busto Arsizio Hospital | Ricci E.,Luigi Sacco Hospital | Carenzi L.,Luigi Sacco Hospital | And 6 more authors.
AIDS | Year: 2012

Central nervous system (CNS) symptoms have been reported in clinical trials and case reports in patients receiving raltegravir. We investigated CNS symptoms in 453 HIV-infected patients. Of these 47 (10.4%) developed at least one drug-related CNS symptom. Predictors of CNS symptoms were concomitant therapy with tenofovir or with proton pump inhibitors that can increase raltegravir concentration. Thus, our data suggest a possible correlation between high raltegravir plasma concentrations and CNS symptoms, and therefore their monitoring in clinical practice. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Nseir W.,Unit of Infectious Diseases | Khateeb J.,Unit of Infectious Diseases | Abu-Elheja O.,Holy Family Hospital | Jihad B.,Rabin Medical Center | And 3 more authors.
Infection | Year: 2012

Background: The aim of this investigation was to assess the effect of prior statin use on the 30-day in-hospital mortality among bacteraemic patients and to determine the impact of long-term versus short-term statin use on the mortality of bacteraemic patients. Patients and methods: A retrospective study of 342 bacteraemic patients who presented to the emergency department (ED) within a period of 7 years was undertaken. Twenty-three patients did not meet the inclusion criteria. The remaining 319 patients were divided into three groups according to statin use and duration of therapy prior to the bacteraemic episode: group 1 (n = 123) had long-term statin use ≥12 weeks, group 2 (n = 35) had short-term statin use <12 weeks, and group 3 (n = 161) had no statin use. Results: The overall 30-day in-hospital all-cause mortality of patients with statins was lower than patients without statin therapy (13 vs. 24%, p = 0.001). The mortality rate in group 1 was lower than in group 2 (11 vs. 17%, p = 0.04). After adjusting for confounding variables, the results of a multiple Cox regression analysis revealed that the absence of statin use (hazard ratio [HR] = 2.98; 95% confidence interval [CI] 1.59-5.56, p = 0.001) was associated with increased 30-day in-hospital all-cause mortality in bacteraemic patients. Conclusions: Statins reduce the 30-day in-hospital all-cause mortality of bacteraemic patients. Long-term statin use prior to the bacteraemia improves the survival of bacteraemic patients more than short-term statin use. © 2011 Springer-Verlag.

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