Lung Compartmentalization of Increased TNF Releasing Ability by Mononuclear Phagocytes in Pulmonary Sarcoidosis

The TNF is a monokine with cytotoxic and tumor-necrosing activities; in addition, TNF may play a role in inflammatory processes. The present study evaluates spontaneous and LPS-mediated release of TNF by AMs and autologous peripheral BMs of normal subjects and patients with pulmonary sarcoidosis. A recently developed cytotoxicity assay, specific for detection of TNF activity, was applied. This study demonstrates that (1) unstimulated mononuclear phagocytes released low levels of TNF with no differences between groups; (2) when effector cells were stimulated with LPS, AMs from patients with active pulmonary sarcoidosis released more TNF than AMs recovered from normal subjects and from patien…

Effect of indomethacin on the kinetics of tumour necrosis factor alpha release and tumour necrosis factor alpha gene expression by human blood monocytes

Summary In this investigation we have examined the effects of indomethacin, an inhibitor of the cyclooxygenase pathway of arachidonic acid, upon the kinetics of the release of tumour necrosis factor alpha (TNF) and of the expression of TNF gene by lipopolysaccharide (LPS)-stimulated human blood monocytes (BM). Following stimulation of BM with LPS, TNF was released within 2 h, reached peak values at 8 h and declined at subsequent time-points (24 and 48 h). Indomethacin (10−5 m ) slightly stimulated the production of TNF at 2, 4, and 8 h and prevented the decline of TNF observed at 24 and 48 h. This effect was related to the persistence of TNF synthesis, as demonstrated by kinetics evaluation…

ICAM-1 and α3β1 expression by bronchial epithelial cells and theirin vitromodulation by inflammatory and anti-inflammatory mediators

Background: Adhesion molecules are involved in inflammatory and repair processes of the bronchial epithelium. ICAM-1 is mainly involved in inflammatory reactions, whereas integrins, such as α3β1, are mainly involved in repair processes. Methods: Using bronchial biopsies from 10 asthmatics and eight controls, we first evaluated by immunohistochemistry expression of α3β1 and ICAM-1 in intact and damaged epithelium. Then, using the human pulmonary epithelial cell line WI-26 VA, we studied, by flow-cytometry, the modulation of ICAM-1 and α3β1 expression, and, by ELISA, the release of fibronectin by proinflammatory cytokines, such as IL-5, and anti-inflammatory cytokines, such as IL-4, TGF-β, an…

MODULATING ALLERGIC RESPONSE BY UNLOCKING THE STRUCTURE OF THE MAJOR PARIETARIA ALLERGENS

Fine characterization of immunological mechanisms mediated by the major allergens of Parietaria judaica and hypoallergenic hybrid, rPjEDcys

Purpose: Allergy is a hypersensitivity disease IgE-mediated, affecting more than 25% of the population. The symptoms of IgE-mediated allergies reactions can be transiently ameliorated pharmacologically, but the only curative treatment of allergies is Allergen-Specific Immunotherapy (SIT). Recombinant hypoallergenic allergen derivatives with reduced allergenic activity have been engineered to reduce side effects during SIT. Parietaria judaica (Pj) pollen contains two major allergens belonging to the family of Lipid Tranfer Proteins (Par j 1 and Par j 2). By means of DNA recombinant technology, a hybrid hypoallergenic (PjEDcys), expressing disulphide bond variants of Par j 1 and Par j 2, was …

Improvement of ALT decay kinetics by all-oral HCV treatment: Role of NS5A inhibitors and differences with IFN-based regimens

Background Intracellular HCV-RNA reduction is a proposed mechanism of action of direct-acting antivirals (DAAs), alternative to hepatocytes elimination by pegylated-interferon plus ribavirin (PR). We modeled ALT and HCV-RNA kinetics in cirrhotic patients treated with currently-used all-DAA combinations to evaluate their mode of action and cytotoxicity compared with telaprevir (TVR)+PR. Study design Mathematical modeling of ALT and HCV-RNA kinetics was performed in 111 HCV-1 cirrhotic patients, 81 treated with all-DAA regimens and 30 with TVR+PR. Kinetic-models and Cox-analysis were used to assess determinants of ALT-decay and normalization. Results HCV-RNA kinetics was biphasic, reflecting …