Document Detail


Anti-IL-5 (mepolizumab) therapy reduces eosinophil activation ex vivo and increases IL-5 and IL-5 receptor levels.
MedLine Citation:
PMID:  18410960     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Anti-IL-5 might be a useful therapeutic agent for eosinophilic disorders, yet its immunologic consequences have not been well characterized.
OBJECTIVE: We sought to characterize the hematologic and immunologic effects of anti-IL-5 in human subjects.
METHODS: The effects of 3-month infusions of mepolizumab were assessed in 25 patients with a variety of eosinophilic syndromes. Samples with increased IL-5 levels after therapy were analyzed by using size exclusion filtration. Immunoreactive IL-5 fraction and plasma samples were subsequently precipitated with saturating concentrations of protein A/G.
RESULTS: Twenty-three patients responded to anti-IL-5 therapy with a decrease in blood eosinophil counts and a reduced percentage of CCR3(+) cells by 20- and 13-fold, respectively (P < .0001). Responsiveness was not related to the levels of baseline plasma IL-5 or the presence of FIP1L1-PDGFRA fusion gene. Persistently decreased blood eosinophilia remained for 3 months after final infusion in 76% of subjects. Therapy was associated with a large increase in blood IL-5 levels, likely because of a circulating IL-5/mepolizumab complex precipitated with protein A/G, a significant increase in eosinophil IL-5 receptor alpha expression, and increased percentage of CD4(+) and CD8(+) cells producing intracellular IL-5 (P < .05). Additionally, anti-IL-5 therapy decreased eotaxin-stimulated eosinophil shape change ex vivo.
CONCLUSIONS: Anti-IL-5 therapy induces a dramatic and sustained decrease in blood eosinophilia (including CCR3(+) cells), decreased eosinophil activation, and increased circulating levels of IL-5 in a variety of eosinophilic disorders. Increased levels of IL-5 receptor alpha and lymphocyte IL-5 production after anti-IL-5 therapy suggest an endogenous IL-5 autoregulatory pathway.
Authors:
Miguel L Stein; Joyce M Villanueva; Bridget K Buckmeier; Yoshiyuki Yamada; Alexandra H Filipovich; Amal H Assa'ad; Marc E Rothenberg
Publication Detail:
Type:  Clinical Trial, Phase I; Clinical Trial, Phase II; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2008-04-14
Journal Detail:
Title:  The Journal of allergy and clinical immunology     Volume:  121     ISSN:  1097-6825     ISO Abbreviation:  J. Allergy Clin. Immunol.     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-06-09     Completed Date:  2008-07-01     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  1275002     Medline TA:  J Allergy Clin Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1473-83, 1483.e1-4     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Antibodies, Monoclonal / therapeutic use*
Antibodies, Monoclonal, Humanized
Cytokines / biosynthesis
Enzyme-Linked Immunosorbent Assay
Eosinophilia / blood,  drug therapy*
Eosinophils / drug effects*
Female
Flow Cytometry
Fluorescent Antibody Technique
Humans
Interleukin-5 / antagonists & inhibitors,  blood*
Male
Middle Aged
Receptors, Interleukin-5 / blood,  drug effects*
T-Lymphocyte Subsets / drug effects
T-Lymphocytes / drug effects
Grant Support
ID/Acronym/Agency:
FD-R 002313/FD/FDA HHS; M01 RR 08084/RR/NCRR NIH HHS; M01 RR008084/RR/NCRR NIH HHS; M01 RR008084-110217/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antibodies, Monoclonal, Humanized; 0/Cytokines; 0/Interleukin-5; 0/Receptors, Interleukin-5; 0/mepolizumab
Comments/Corrections
Comment In:
J Allergy Clin Immunol. 2009 Jan;123(1):269; author reply 269-70   [PMID:  18951621 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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