levocetirizine and Inflammation

Persistent allergic rhinitis (PER) has a moderate impact on the sense of smell, but no controlled study has reported the effect of antihistamines on the loss of smell in patients with PER.. Patients with PER and subjective loss of the sense of smell (n = 27) were included in this pilot randomised, double-blind, placebo-controlled study. Nasal symptoms, nasal endoscopy, skin prick test, acoustic rhinometry, peak nasal inspiratory flow, nasal nitric oxide (nNO), and olfactometry (Barcelona Smell Test-24; BAST-24) were performed and evaluated in all PER patients at baseline and after 7 and 30 days of treatment with levocetirizine 5 mg or placebo.. The study population was randomized into two homogeneous groups: levocetirizine (n = 14) and placebo groups (n = 13). The evolution of symptoms reflected the therapeutic effect of levocetirizine treatment on rhinorrhea, nasal itching, eye itching, sneezing, and the total symptoms score after 7 and 30 days. Significant improvement in loss of smell by a visual analog scale (VAS) was observed after 7 days of levocetirizine treatment (7.2 ± 4.3; p < 0.05) compared to placebo (-9.4 ± 6.2). Improvement in smell identification by BAST-24 was strongly correlated (r = 0.72; p < 0.05) with smell improvement by VAS after 30 days. After 7 days of treatment with levocetirizine, the nNO values decreased (-494 ± 188) compared to placebo (155 ± 284 ppb; p < 0.05).. The CIRANO study suggests that levocetirizine is effective on PER symptoms, including a transient improvement in loss of smell, and that this improvement concurs more with reduction of nasal inflammation than of nasal patency.

Topics: Adult; Cetirizine; Double-Blind Method; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Inflammation; Male; Nitric Oxide; Olfaction Disorders; Placebos; Rhinitis, Allergic, Seasonal; Smell

Allergic rhinitis is a high-prevalence disease that affects quality of life (QOL), sleep quality and productivity of patients. According to the ARIA initiative, it is classified as intermittent and persistent, the latter being the most troublesome.. The aim of this randomized, open-label, 6-month, pilot study was to determine whether levocetirizine 5 mg administered continuously once daily in the morning was better than levocetirizine 5 mg on-demand in symptomatic subjects with persistent allergic rhinitis. Total and individual symptom scores were recorded in a diary card throughout the study. QOL, quality of sleep, nasal cytology, rate of drug intake, and safety were also assessed at pre-defined time-points.. In all, adult patients (31 in each group) were enrolled, of whom 22 dropped out. Both treatment regimens considerably decreased the total and individual symptoms scores from baseline and achieved similar levels up to week 14. Continuous treatment was generally better than on-demand from week 15 onwards, reaching statistical significance from weeks 17 to 21 (from week 19 to 21 for nasal pruritus). Both regimens substantially improved QOL and sleep quality. Both treatments were well tolerated, although the on-demand group reported more adverse events.. The present open label study in 62 patients indicates that levocetirizine 5 mg reliably controls persistent rhinitis over a period of 6 months, and shows a trend to be more effective in controlling the symptoms of rhinitis, improving QOL and decreasing nasal inflammation, when administered as long-term continuous therapy rather than as on-demand therapy.

Topics: Adult; Aged; Cetirizine; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Inflammation; Male; Middle Aged; Pilot Projects; Quality of Life; Rhinitis, Allergic, Perennial; Time Factors

Nasal obstruction is the main symptom in patients with perennial allergic rhinitis. Some new antihistamines have been demonstrated to be capable of improving this symptom.. The aim of this pilot study was to evaluate nasal symptoms, nasal airflow, eosinophils, and IL-4 in patients with perennial allergic rhinitis, before and after treatment with two new antihistamines: desloratadine and levocetirizine.. Thirty patients with perennial allergic rhinitis were evaluated, 26 males and 4 females (mean age 26+/-7.1 years). All of them received either desloratadine (5 mg/daily) or levocetirizine (5 mg/daily) or placebo for 4 weeks. The study was double-blind, parallel-group, placebo-controlled, and randomized. Total symptom score (including: rhinorrhea, nasal itching, sneezing, and nasal obstruction) was assessed before and after treatment. Rhinomanometry and decongestion test, nasal lavage, and nasal scraping were performed in all subjects before and after treatment. Eosinophils were counted by conventional staining; IL-4 was measured by immunoassay of fluids recovered from nasal lavage.. Desloratadine and levocetirizine treatment induced significant symptom relief and significant reduction of IL-4. Both antihistamines significantly affected all parameters in comparison with placebo.. This pilot study demonstrates the effectiveness of antihistaminic treatment in: i) relieving nasal symptoms, including obstruction, ii) improving nasal airflow, iii) exerting decongestant activity, iv) reducing eosinophil infiltration, and v) diminishing IL-4 levels.

Topics: Adolescent; Adult; Cetirizine; Double-Blind Method; Eosinophils; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Inflammation; Interleukin-4; Leukocyte Count; Loratadine; Male; Nasal Lavage Fluid; Nasal Mucosa; Nasal Obstruction; Pilot Projects; Piperazines; Rhinitis, Allergic, Perennial; Rhinomanometry

This protocol describes microsphere-based protease assays for use in flow cytometry and high-throughput screening. This platform measures a loss of fluorescence from the surface of a microsphere due to the cleavage of an attached fluorescent protease substrate by a suitable protease enzyme. The assay format can be adapted to any site or protein-specific protease of interest and results can be measured in both real time and as endpoint fluorescence assays on a flow cytometer. Endpoint assays are easily adapted to microplate format for flow cytometry high-throughput analysis and inhibitor screening.

Topics: Animals; Biotinylation; Flow Cytometry; Fluorescence Resonance Energy Transfer; Green Fluorescent Proteins; High-Throughput Screening Assays; Humans; Inflammation; Kinetics; Microspheres; Peptide Hydrolases; Peptides; Reproducibility of Results; Temperature

Keratinocytes participate in initiation and amplification of T-cell-mediated skin diseases. During these disorders, histamine can be released from both residents skin cells and immigrating leukocytes, and can affect the functions of dendritic cells, monocytes, and lymphocytes. Little information is available on the effects of histamine on keratinocytes.. To examine the presence of functional H1 receptors on human keratinocytes and the capacity of histamine to modulate the expression of inflammatory molecules in these cells.. Primary cultures of resting and cytokine-activated keratinocytes from healthy subjects were analyzed for histamine H1 receptor expression and the production of inflammatory mediators after exposure to histamine receptor agonists and antagonists.. Cultured keratinocytes constitutively expressed the H1 receptor mRNA and protein, which was not influenced by IFN-gamma, TNF-alpha, or IL-4. H1 but not H2 agonists induced calcium fluxes in keratinocytes. Treatment of keratinocytes with histamine (10 -7 to 10 -4 mol/L) or beta-histine increased the IFN-gamma-induced expression of membrane intercellular adhesion molecule 1 and MHC class I but not MHC class II molecules. Moreover, H1 stimulation promoted basal CC chemokine ligand (CCL)-5/RANTES and GM-CSF secretion and augmented IFN-gamma-induced release of the chemokines CCL2/monocyte chemoattractant protein 1, CCL5/RANTES, CCL20/macrophage inflammatory protein 3alpha, and CXC chemokine ligand 10/IFN-induced protein of 10 kd, as well as GM-CSF. Administration of the H1 antihistamine levocetirizine, but not of the H2 antihistamine cimetidine, abolished histamine-dependent expression of all of the investigated proinflammatory molecules in a dose-dependent manner (0.01-10 mumol/L). Levocetirizine at higher doses also reduced intercellular adhesion molecule 1, CCL5/RANTES, and GM-CSF release induced solely by IFN-gamma.. Histamine exerts proinflammatory effects on keratinocytes via the H1 receptor, and these effects are efficiently inhibited by levocetirizine.

Topics: Adult; Cells, Cultured; Cetirizine; Chemokines; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Histamine; Humans; Inflammation; Intercellular Adhesion Molecule-1; Interferon-gamma; Keratinocytes; Male; Piperazines; Receptors, Histamine H1