Background: Very late antigen (VLA-4) antagonists have been proposed as potential therapies for diseases in which cell recruitment and accumulation are causative. Asthma, which is characterized by airway inflammation involving the accumulation of eosinophils and mononuclear cells, is one such disease.
Objective: We sought to assess the effect of IVL745, a VLA-4 antagonist, on the early and late asthmatic response (LAR) and on markers of airway inflammation after allergen inhalation.
Methods: The study was of a placebo-controlled, double-blind, randomized, 2-way crossover design. Sixteen subjects with mild-to-moderate asthma controlled with short-acting beta2-agonists only and with a LAR to inhaled allergen participated in the study. At one treatment period they took 20 mg of IVL745 and one treatment period placebo. Both treatments were taken twice daily for 7 days, with a single dose on day 8. Treatments were separated by a washout period of at least 2 weeks. On day 7 of each treatment period, sputum was induced and collected, and exhaled nitric oxide (NO) was measured. On day 8, an inhaled bolus allergen challenge was performed, and blood was taken for pharmacokinetics. On day 9, exhaled NO was measured, and a methacholine challenge was done. On day 10, sputum was induced and collected. Adverse events, peak expiratory flow (PEF), use of short-acting beta2-agonists, and asthma symptoms were recorded daily throughout the study.
Results: There was no statistically significant difference between IVL745 and placebo in the effect on the LAR after allergen challenge, as measured by the area under the curve of the percentage change in FEV1 from the prechallenge baseline (mean [SEM], -81.99 [18.80] after IVL745 and -72.58 [21.29] after placebo; 95% CI of difference, -36 to 16.8; P = .46) or by the maximum percentage change from the prechallenge baseline (mean [SEM], -23.44 [4.73] after IVL745 and -21.30 [5.17] after placebo; 95% CI of difference, -11 to 6.29; P = .60). There was a statistically significant decrease in the percentage of eosinophils in sputum on day 7 of treatment with IVL745 (mean [SEM], 7.32 [1.46]) compared with placebo (mean [SEM], 15.00 [1.92]; 95% CI of difference, -13 to -1.2; P = .02). There was no statistically significant difference between IVL745 and placebo with respect to the early asthmatic response, methacholine hyperresponsiveness, exhaled NO, postallergen sputum, symptoms, inhaled beta2-agonist use, or PEF.
Conclusion: In patients with mild-to-moderate atopic asthma, IVL745 did not affect the early and late response to inhaled allergen or markers of airway inflammation, except for a modest reduction in sputum eosinophils.
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http://dx.doi.org/10.1016/j.jaci.2005.04.045 | DOI Listing |
PLoS One
January 2025
Research Service and Pulmonary Section Medical Service, Veterans Affairs Ann Arbor Health System, Ann Arbor, Michigan, United States of America.
Deployment-related constrictive bronchiolitis (DRCB) has emerged as a health concern in military personnel returning from Southwest Asia. Exposure to smoke from a fire at the Al-Mishraq sulfur enrichment facility and/or burn pits was reported by a subset of Veterans diagnosed with this disorder. DRCB is characterized by thickening and fibrosis of small airways (SA) in the lung, but whether these are related to toxin inhalation remains uncertain.
View Article and Find Full Text PDFAdv Healthc Mater
January 2025
Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China.
Eosinophils play a crucial role as effector cells in asthma pathogenesis, with their differentiation being tightly regulated by metabolic mechanisms. While the involvement of iron in various cellular processes is well known, its specific role in eosinophil differentiation has largely remained unexplored. This study demonstrates that iron levels are increased during the differentiation process from eosinophil progenitors to mature and activated eosinophils in the context of allergic airway inflammation.
View Article and Find Full Text PDFCells
January 2025
Molecular and Cell Biology Unit, Department of Pediatric Pulmonology, Allergy and Clinical Immunology, Poznan University of Medical Sciences, 60-572 Poznan, Poland.
Asthma is a major non-communicable disease whose pathogenesis is still not fully elucidated. One of the asthma research models is precision-cut lung slices (PCLSs), and among the therapeutic options, miRNA molecules are of great interest. The aim of our study was to investigate whether inhibition of miR-223-3p and miR328a-3p affects the inflammatory response in PCLSs derived from a rat with HDM-induced allergic inflammation and a control rat.
View Article and Find Full Text PDFJ Microbiol Biotechnol
December 2024
Institute of Agricultural Science and Technology, Kyungpook National University, Daegu 41566, Republic of Korea.
L. (noni) is native to the tropical and semitropical areas and has been commercially available in health food stores and chain grocery stores specializing in natural foods, recently. Noni seeds are discarded as waste products through the industrial production of noni juice even though their bioactivity components might be a potential source of functional foods.
View Article and Find Full Text PDFPLoS Pathog
January 2025
Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, Georgia, United States of America.
The continued evolution of SARS-CoV-2 variants capable of subverting vaccine and infection-induced immunity suggests the advantage of a broadly protective vaccine against betacoronaviruses (β-CoVs). Recent studies have isolated monoclonal antibodies (mAbs) from SARS-CoV-2 recovered-vaccinated donors capable of neutralizing many variants of SARS-CoV-2 and other β-CoVs. Many of these mAbs target the conserved S2 stem region of the SARS-CoV-2 spike protein, rather than the receptor binding domain contained within S1 primarily targeted by current SARS-CoV-2 vaccines.
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