Search results for "interleukin-5"
showing 10 items of 32 documents
Treating severe asthma:Targeting the IL‐5 pathway
2021
Abstract Severe asthma is a heterogeneous disease with different phenotypes based on clinical, functional or inflammatory parameters. In particular, the eosinophilic phenotype is associated with type 2 inflammation and increased levels of interleukin (IL)‐4, IL‐5 and IL‐13). Monoclonal antibodies that target the eosinophilic inflammatory pathways (IL‐5R and IL‐5), namely mepolizumab, reslizumab, and benralizumab, are effective and safe for severe eosinophilic asthma. Eosinophils threshold represents the most indicative biomarker for response to treatment with all three monoclonal antibodies. Improvement in asthma symptoms scores, lung function, the number of exacerbations, history of late‐o…
Lung CD11c+ cells from mice deficient in Epstein-Barr virus-induced gene 3 (EBI-3) prevent airway hyper-responsiveness in experimental asthma
2007
Epstein-Barr virus-induced gene (EBI)-3 codes for a soluble type 1 cytokine receptor homologous to the p40 subunit of IL-12 that is expressed by antigen-presenting cells following activation. Here, we analyzed the functional role of EBI-3 in a murine model of asthma associated with airway hyper-responsiveness (AHR) in ovalbumin-sensitized mice. Upon allergen challenge, EBI-3-/- mice showed less severe AHR, decreased numbers and degranulation of eosinophils and a significantly reduced number of VCAM-1+ cells in the lungs as compared to wild-type littermates. We thus analyzed lung CD11c+ cells before and after allergen challenge in these mice and found that before allergen challenge, lung CD1…
Eosinophil-selective mediators in human strongyloidiasis
2006
SUMMARY Strongyloides stercoralis infection is characterized by the production of IgE and eosinophils in peripheral blood. Experimental studies have demonstrated that eosinophils play an important role in protection against Strongyloides stercoralis, but the mechanisms regulating eosinophils are not known. In this study we have focused on analysing the molecules that selectively regulate eosinophil migration, namely eotaxin and interleukin-5 (IL-5), using an enzyme-linked immunosorbent assay in patients with strongyloidiasis. Serum expression of eotaxin and IL-5 were significantly increased in patients compared with the control group. This rise suggests that selective mediators of the eosin…
Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial
2012
BACKGROUND: Some patients with severe asthma have recurrent asthma exacerbations associated with eosinophilic airway inflammation. Early studies suggest that inhibition of eosinophilic airway inflammation with mepolizumab-a monoclonal antibody against interleukin 5-is associated with a reduced risk of exacerbations. We aimed to establish efficacy, safety, and patient characteristics associated with the response to mepolizumab. METHODS: We undertook a multicentre, double-blind, placebo-controlled trial at 81 centres in 13 countries between Nov 9, 2009, and Dec 5, 2011. Eligible patients were aged 12-74 years, had a history of recurrent severe asthma exacerbations, and had signs of eosinophil…
Interleukin-5 production by mononuclear cells from aged individuals: implication for autoimmunity.
1999
It is well known that in the elderly a deterioration of immune functions may occur. Particularly, stimulation of T cells from aged individuals leads to different kind and/or size of responses if compared with the responses obtained from T cells from young individuals. At the same time, an increase in prevalence of autoantibodies occurs in elderly. The altered production of certain cytokines might explain this paradox of decreased responsiveness to foreign antigens in the face of an increased response to self-antigens. We and others have suggested that this kind of immune response might depend on an age-associated impairment of Th-1 type function that selectively affects production of cytoki…
Assessment of the long-term safety of mepolizumab and durability of clinical response in patients with severe eosinophilic asthma
2018
Background Mepolizumab has demonstrated favorable safety and efficacy profiles in placebo-controlled trials of 12 months' duration or less; however, long-term data are lacking. Objective We sought to evaluate the long-term safety and efficacy of mepolizumab in patients with severe eosinophilic asthma (SEA). Methods COLUMBA (Open-label Long Term Extension Safety Study of Mepolizumab in Asthmatic Subjects, NCT01691859 ) was an open-label extension study in patients with SEA previously enrolled in DREAM (Dose Ranging Efficacy And Safety With Mepolizumab in Severe Asthma, NCT01000506 ). Patients received 100 mg of subcutaneous mepolizumab every 4 weeks plus standard of care until a protocol-def…
Homodimeric murine interleukin-3 agonists indicate that ligand dimerization is important for high-affinity receptor complex formation.
1994
Homodimeric murine interleukin 3 (mIL-3) agonists were generated by intermolecular cystine-bonding. Steady-state binding assays and association kinetics performed at 4 degrees C using these agonists revealed specific binding to both the high- and low-affinity receptor. DSS-mediated crosslinking studies performed at 4 degrees C with agonist concentrations compatible with high-affinity receptor complex formation allowed to detect protein complexes of the alpha chain, the beta chain(s) and the high-affinity receptor complex migrating with apparent molecular weights of 90 kDa, 140 kDa, and above 180 kDa, respectively. In contrast, monomeric mIL-3 was crosslinked to the alpha chain receptor only…
Dual role of interleukin-1alpha in delayed-type hypersensitivity and airway hyperresponsiveness.
2009
<i>Background:</i> Using a T helper (Th)1/Th2 disease model, we previously showed that genetically determined Th development depends on dendritic cell-derived interleukin (IL)-1α. In <i>Leishmania major</i> infections, Th1 immunity develops if IL-1α is present during T cell priming, whereas at later time points, IL-1α worsens disease outcome. In the present study, we determined the role of IL-1α in other Th2-mediated diseases. <i>Methods:</i> BALB/c mice were subjected to delayed-type hypersensitivity (DTH) or ovalbumin (OVA)/alum-induced allergic asthma in the presence or absence of IL-1α. <i>Results:</i> In DTH, mice treated with IL-1α durin…
Oral delivery of homologous and heterologous strains of rotavirus to BALB/c mice induces the same profile of cytokine production by spleen cells.
1998
Abstract In this work, we wanted to clarify if differences in antibody (Ab) and particularly in secretory immunoglobulin A (IgA) responses following homologous or heterologous rotavirus infection could be explained by different priming of specific T helper (Th) cells. We compared the Ab responses from suckling BALB/c mice orally inoculated with either a heterologous simian (SA11) or bovine (RF) rotavirus or a homologous murine rotavirus (EHP w ), as well as the profile of cytokines produced by spleen cells after in vitro restimulation. Oral inoculation of EHP w and SA11 induced a similar pattern of Ab with mucosal and serum IgA associated with serum IgG with equal levels of IgG1 and IgG2a, …
Inhibition of human allergic T-cell responses by IL-10–treated dendritic cells: Differences from hydrocortisone-treated dendritic cells
2001
Abstract Background: Dendritic cells (DCs) are able to induce human allergic T H 1 responses as well as T H 2 responses. Objective: In this study, we examined the effect of antiinflammatory agents such as IL-10 and hydrocortisone (HC) on the accessory function of DCs and the resulting T-cell response, especially that of T H 2 cells. Methods: Naive and memory CD4 + T cells from atopic donors were stimulated with autologous allergen-pulsed DCs generated from CD14 + monocytes by culture with GM-CSF/IL-4 and fully matured with IL-1β, TNF-α, and PGE 2 in the presence or absence of IL-10 or HC. Results: IL-10–treated DCs and, to a lesser extent, HC-treated DCs showed a decreased expression of MHC…