Anna Maria Riccio

Terfenadine and fexofenadine reduce in vitro ICAM-1 expression on human continuous cell lines.

BACKGROUND Epithelial cells and fibroblasts play an important role in allergic inflammation. Modulation of surface expression of adhesion molecules on epithelial cells by antiallergic drugs has been shown by both in vivo and in vitro studies. OBJECTIVE The aim of the study was to evaluate the effect exerted by terfenadine and fexofenadine on adhesion molecules expression (CD54/ICAM-1 and CD29) of a human continuously cultured conjunctival epithelial cell line (WK) and a fibroblast cell line (HEL). METHODS By means of flow cytometry analysis, we evaluated ICAM-1 and CD29 expression by WK and HEL epithelial cells in basal condition (at baseline) or after IFN gamma or TNF alpha stimulation in the presence or in the absence of terfenadine and fexofenadine. We also performed immunoenzymatic assays in order to evaluate soluble ICAM-1 released by WK cells and procollagen type I and III and IL6 released by HEL cells. RESULTS Terfenadine and fexofenadine significantly reduced ICAM-1 basal expression on WK cells at the concentration of 1 microg/mL and 50 microg/mL, respectively. In addition, both terfenadine and fexofenadine were able to decrease soluble ICAM-1 levels in IFN gamma-stimulated WK cells. On HEL fibroblasts, fexofenadine only was able to inhibit ICAM-1 upregulation induced by IFN gamma. Concerning the release of fibroblast products, we observed a dose-dependent decrease of spontaneous IL6 release only in the presence of fexofenadine. CONCLUSION This study shows that terfenadine and fexofenadine exert a biologic effect directly on epithelial cells and fibroblasts reducing ICAM-1 expression and partially reducing soluble ICAM-1 release.

Nasal endoscopy in asthmatic children: Assessment of rhinosinusitis and adenoiditis incidence, correlations with cytology and microbiology

Background Upper respiratory airway diseases may induce a worsening of asthma. Sinusitis represents one of the most common chronic diseases. The association of asthma and sinusitis varies greatly in different studies, depending on diagnostic procedures.

Cytokine pattern in allergic and non-allergic chronic rhinosinusitis in asthmatic children

Background Rhinosinusitis represents one of the most common chronic diseases. The association of rhinosinusitis with asthma has been frequently reported. Eosinophils and Th2 cells play a pathogenic mechanism in asthma.

Intercellular adhesion molecule-1 on cultured human epithelial cell lines: influence of proinflammatory cytokines

Paolieri F, Battifora M, Riccio AM, Pesce G, Canonica GW, Bagnasco M. Intercellular adhesion molecule‐1 on cultured human epithelial cell lines: influence of proinflammatory cytokines.

Seasonal rhinitis and azelastine: Long- or short-term treatment☆☆☆★★★

BACKGROUND Azelastine is a topical antihistamine, clinically demonstrated to be effective in allergic rhinitis. OBJECTIVE We evaluated the clinical efficacy and the antiallergic activity of azelastine nasal spray, administered 0.56 mg per day, 0.28 mg per day, or on demand over a 3-month period during natural allergen exposure, in a double-blind, placebo-controlled fashion. METHODS Thirty patients, sensitized to grass or Parietaria pollen, were allocated to three treatment groups: those receiving the standard dosage (0.14 mg/nostril two times a day), half the dosage (0.07 mg/nostril two times a day), or placebo daily for 3 months. All patients were allowed to take additional doses of azelastine when needed. Evaluation parameters were as follows: clinical symptoms recorded on a diary card, number of additional, on-demand azelastine puffs, nasal inflammatory cell count, intercellular adhesion molecule-1 expression on nasal epithelial cells, and pollen count. RESULTS This study showed the following: (1) the half dose (0.28 mg/day) and the standard dose (0.56 mg/day) were equally effective in reducing clinical symptoms (p = NS), although the standard dosage required fewer additional puffs during times of peak pollen counts (p < 0.05); (2) both dosages were able to reduce the allergic inflammation (p < 0.05 vs placebo); and (3) on-demand use achieved acceptable clinical control but did not significantly reduce allergic inflammation. CONCLUSION Continuous treatment was more effective than on-demand use as assessed by both clinical evaluation and antiinflammatory action.

Cetirizine treatment of rhinitis in children with pollen allergy: evidence of its antiallergic activity

Background Cetirizine is an antihistamine, largely used in the treatment of allergic rhinoconjunctivitis, which also exerts anti‐allergic activity.

Proteomics of bronchial biopsies: Galectin-3 as a predictive biomarker of airway remodelling modulation in omalizumab-treated severe asthma patients

Asthma is a chronic inflammatory disease. Reticular basement membrane (RBM) thickening is considered feature of airway remodelling (AR) particularly in severe asthma (SA). Omalizumab, mAb to IgE is effective in SA and can modulate AR. Herein we describe protein profiles of bronchial biopsies to detect biomarkers of anti-IgE effects on AR and to explain potential mechanisms/pathways. We defined the bronchial biopsy protein profiles, before and after treatment. Unsupervised clustering of baseline proteomes resulted in very good agreement with the morphometric analysis of AR. Protein profiles of omalizumab responders (ORs) were significantly different from those of non-omalizumab responders (NORs). The major differences between ORs and NORs lied to smooth muscle and extra cellular matrix proteins. Notably, an IgE-binding protein (galectin-3) was reliable, stable and predictive biomarker of AR modulation. Omalizumab down-regulated bronchial smooth muscle proteins in SA. These findings suggest that omalizumab may exert disease-modifying effects on remodelling components.

Effects of fexofenadine and other antihistamines on components of the allergic response: Adhesion molecules

Intercellular adhesion molecules (ICAMs), in particular ICAM-1, appear to play a crucial role in the recruitment and migration of inflammatory cells to the site of an allergic reaction. Glucocorticoids and allergen-specific immunotherapy have been shown to exert effects on selected components of this system, both in vitro and in vivo, but further research is required to better understand the effects of these therapies. Nasal and conjunctival challenge models (including natural and experimental allergen exposure) represent useful and safe tools for studying the activity of antiallergy drugs in vivo. These tests allow the investigation of a wide variety of parameters including inflammatory infiltrate, ICAM-1 expression, and changes in the concentration of soluble inflammatory mediators. With these tools, anti-inflammatory activity related to the modulation of epithelial cell adhesion molecules has been demonstrated in vivo for several H(1)-receptor antagonists (azelastine, cetirizine, loratadine, levocabastine, oxatomide, and terfenadine). Fexofenadine is a nonsedating, long-acting antihistamine with highly selective H(1)-receptor antagonist activity and a particularly favorable safety profile. In addition, fexofenadine has proven anti-inflammatory activity and has been shown to inhibit a number of mediators at clinically relevant concentrations, including in vitro inhibition of ICAM-1 expression on conjunctival and nasal epithelial cells.

Preclinical development of a novel class of CXCR4 antagonist impairing solid tumors growth and metastases.

The CXCR4/CXCL12 axis plays a role in cancer metastases, stem cell mobilization and chemosensitization. Proof of concept for efficient CXCR4 inhibition has been demonstrated in stem cell mobilization prior to autologous transplantation in hematological malignancies. Nevertheless CXCR4 inhibitors suitable for prolonged use as required for anticancer therapy are not available. To develop new CXCR4 antagonists a rational, ligand-based approach was taken, distinct from the more commonly used development strategy. A three amino acid motif (Ar-Ar-X) in CXCL12, also found in the reverse orientation (X-Ar-Ar) in the vMIP-II inhibitory chemokine formed the core of nineteen cyclic peptides evaluated for inhibition of CXCR4-dependent migration, binding, P-ERK1/2-induction and calcium efflux. Peptides R, S and I were chosen for evaluation in in vivo models of lung metastases (B16-CXCR4 and KTM2 murine osteosarcoma cells) and growth of a renal cells xenograft. Peptides R, S, and T significantly reduced the association of the 12G5-CXCR4 antibody to the receptor and inhibited CXCL12-induced calcium efflux. The four peptides efficiently inhibited CXCL12-dependent migration at concentrations as low as 10 nM and delayed CXCL12-mediated wound healing in PES43 human melanoma cells. Intraperitoneal treatment with peptides R, I or S drastically reduced the number of B16-CXCR4-derived lung metastases in C57/BL mice. KTM2 osteosarcoma lung metastases were also reduced in Balb/C mice following CXCR4 inhibition. All three peptides significantly inhibited subcutaneous growth of SN12C-EGFP renal cancer cells. A novel class of CXCR4 inhibitory peptides was discovered. Three peptides, R, I and S inhibited lung metastases and primary tumor growth and will be evaluated as anticancer agents.

Levocetirizine in persistent allergic rhinitis and asthma: effects on symptoms, quality of life and inflammatory parameters

Background Levocetirizine (LCZ) has been shown to be effective in allergic rhinitis. We evaluated its clinical efficacy, antinflammatory actions and its effects on quality of life (QoL) with a specific instrument in the asthma–rhinitis comorbidity.