Effects of interleukin-6 receptor blockade on allergen-induced airway responses in mild asthmatics.

Background: Interleukin (IL)-6 signalling has been implicated in allergic asthma by animal, genetic association and clinical studies. In this study, we tested the hypothesis that tocilizumab (TCZ), a human monoclonal antibody that blocks IL-6 signalling, can prevent the development of allergen-induced bronchoconstriction in humans.

Methods: We performed a randomised, double-blind, placebo-controlled study, with eligible participants completing two allergen inhalation challenge tests, conducted before and after treatment with a single dose of TCZ or placebo.

Achieving "Zero" Defects for Visible Particles in Injectables.

The reduction of visible particles in injectable products is an important element in the consistent delivery of high-quality parenteral products. An important part of this effort is the control of particles that may emanate from the primary packaging materials. The (), with the support of the Pharmaceutical Manufacturers Forum (PMF), has undertaken the task of developing test methods to assess the cleanliness of primary packaging components used in the manufacturing of sterile injectable products.

Feasibility of a portable X-ray fluorescence device for bone lead measurements of condor bones.

Lead based ammunition is a primary source of lead exposure, especially for scavenging wildlife. Lead poisoning remains the leading cause of diagnosed death for the critically endangered California condors, which are annually monitored via blood tests for lead exposure. The results of these tests are helpful in determining recent exposure in condors and in defining the potential for exposure to other species including humans.

Allergen-induced Increases in Sputum Levels of Group 2 Innate Lymphoid Cells in Subjects with Asthma.

Rationale: Group 2 innate lymphoid cells (ILC2), a major source of type 2 cytokines, initiate eosinophilic inflammatory responses in murine models of asthma.

Objectives: To investigate the role of ILC2 in allergen-induced airway eosinophilic responses in subjects with atopy and asthma.

Methods: Using a diluent-controlled allergen challenge crossover study, where all subjects (n = 10) developed allergen-induced early and late responses, airway eosinophilia, and increased methacholine airway responsiveness, bone marrow, blood, and sputum samples were collected before and after inhalation challenge.

IL-25 and IL-33 induce Type 2 inflammation in basophils from subjects with allergic asthma.

Background: The alarmin cytokines IL-25 and IL-33 are key promoters of type 2 inflammation. Basophils respond to alarmin cytokines, however the relationship of these cytokines with basophil activation and recruitment in human studies of allergic asthma has not been well characterized. This study investigated the effect of IL-25 and IL-33 on basophils in a model of allergic asthma.

IL-25 Receptor Expression on Airway Dendritic Cells after Allergen Challenge in Subjects with Asthma.

Rationale: IL-25 is an epithelial-derived cytokine, whose effects are mediated by the IL-25 receptor (IL-17RB), and that has been implicated in the pathogenesis of allergic disease and airway viral responses. Airway myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs) are professional antigen-presenting cells. pDCs may play a protective role in asthma and are key players in the innate immune response through recognition of microbial products via Toll-like receptors (TLRs).

Thymic stromal lymphopoietin activation of basophils in patients with allergic asthma is IL-3 dependent.

Background: Thymic stromal lymphopoietin (TSLP) released after antigenic stimulation of allergic asthmatic airways is a key initiator of type 2 inflammation. Basophils are important effectors of allergic inflammation in the airways. Murine basophils have been shown to respond to TSLP independently of IL-3 by increasing functional thymic stromal lymphopoietin receptor (TSLPR) expression.

Inhibition of allergen-induced basophil activation by ASM-024, a nicotinic receptor ligand.

Background: Nicotinic acetylcholine receptors (nAChRs) were identified on eosinophils and shown to regulate inflammatory responses, but nAChR expression on basophils has not been explored yet.

Objective: We investigated surface receptor expression of nAChR α4, α7 and α1/α3/α5 subunits on basophils. Furthermore, we examined the effects of ASM-024, a synthetic nicotinic ligand, on in vitro anti-IgE and in vivo allergen-induced basophil activation.

Evaluation of peroxisome proliferator-activated receptor agonists on interleukin-5-induced eosinophil differentiation.

Peroxisome proliferator-activated receptor (PPAR) agonists have been suggested as novel therapeutics for the treatment of inflammatory lung disease, such as allergic asthma. Treatment with PPAR agonists has been shown to inhibit airway eosinophilia in murine models of allergic asthma, which can occur through several mechanisms including attenuated generation of chemoattractants (e.g.

Comparison of changes in lung function measured by plethymography and IOS after bronchoprovocation.

Aim: Lung function tests are essential for the diagnosis and management of bronchial asthma. Impulse oscillation (IOS) system is an alternative way to measure lung mechanics for some patients. We investigated the relative sensitivities of IOS, body plethysmography and spirometry in detecting allergen- and methacholine-induced bronchoconstriction.

Progenitor egress from the bone marrow after allergen challenge: role of stromal cell-derived factor 1alpha and eotaxin.

Background: CCR3 expression on CD34+ cells mediates migration to eotaxin in vitro. CXCR4 and stromal cell-derived factor (SDF)-1alpha are important for stem cell homing to hemopoietic compartments.

Objective: To study chemokine-mediated progenitor cell traffic in allergic inflammation.

Kinetics of bone marrow eosinophilopoiesis and associated cytokines after allergen inhalation.

Allergen inhalation is associated with increased eosinophil/basophil progenitors in bone marrow 24 hours after allergen inhalation. This study examined the kinetics of eosinophilopoiesis in dual (n = 14), compared with isolated early, responders (n = 12). Dual responders, in contrast to isolated early responders, develop significant sputum and blood eosinophilia and prolonged airway hyperresponsiveness.

Sputum CD34+IL-5Ralpha+ cells increase after allergen: evidence for in situ eosinophilopoiesis.

Eosinophil lineage-committed progenitors increase in the bone marrow of subjects with asthma developing allergen-induced airway hyperresponsiveness and eosinophilia. Also, higher numbers of circulating eosinophil/basophil cfu have been demonstrated 24 hours after allergen inhalation and in bronchial and nasal biopsies of allergic individuals. These cells may undergo in situ eosinophilopoiesis, suggesting that after allergen inhalation, progenitor cells traffic from the bone marrow to the airways, providing an ongoing source of effector cells.

Allergen-induced fluctuation in CC chemokine receptor 3 expression on bone marrow CD34+ cells from asthmatic subjects: significance for mobilization of haemopoietic progenitor cells in allergic inflammation.

There is increasing evidence that primitive progenitors migrate from the bone marrow (BM) via the peripheral circulation to tissue sites where they undergo in situ differentiation to provide a continued source of effector cells, such as eosinophils, during an allergic inflammatory response. To study mechanisms of progenitor cell mobilization in allergic reactions, we investigated fluctuations in the expression of the eotaxin receptor, CC chemokine receptor 3 (CCR3), on CD34+ cells from stable asthmatics following allergen (i.e.