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Effect of tumor necrosis factor antagonism on allergen-mediated asthmatic airway inflammation.

Abstract：

OBJECTIVE:To assess whether tumor necrosis factor (TNF) antagonism can attenuate eosinophilic airway inflammation in patients with mild-to-moderate allergic asthma. DESIGN:Randomized, double-blind, placebo-controlled trial. SETTING:National Institutes of Health (NIH) Clinical Center. PATIENTS:Twenty-six patients with mild-to-moderate allergic asthma, receiving only inhaled beta-2-agonists, who demonstrated both an early and late phase response to inhalational allergen challenge. INTERVENTION:Injection of a soluble TNF receptor (TNFR:Fc, etanercept, Enbrel) or placebo, 25mg subcutaneously, twice weekly for 2 weeks, followed by a bronchoscopic segmental allergen challenge. MEASUREMENTS:The primary outcome measure was whether TNFR:Fc can access the lung and inhibit TNF bioactivity. Secondary outcome measures included pulmonary eosinophilia, Th2-type cytokines, and airway hyperresponsiveness. RESULTS:Anti-TNF therapy was associated with transient hemiplegia in one patient, which resulted in suspension of the study. Data from the 21 participants who completed the study were analyzed. Following treatment, patients receiving anti-TNF therapy had significantly increased TNFR2 levels in epithelial lining fluid (ELF) (P<0.001), consistent with delivery of TNFR:Fc to the lung. TNF antagonism did not attenuate pulmonary eosinophilia and was associated with an increase in ELF IL-4 levels (P=0.033) at 24h following segmental allergen challenge. TNF antagonism was not associated with a change in airway hyperresponsiveness to methacholine. CONCLUSIONS:TNF antagonism may not be effective for preventing allergen-mediated eosinophilic airway inflammation in mild-to-moderate asthmatics. Transient hemiplegia, which may mimic an evolving stroke, may be a potential toxicity of anti-TNF therapy.

journal_name

Respir Med

journal_title

Respiratory medicine

authors

Rouhani FN,Meitin CA,Kaler M,Miskinis-Hilligoss D,Stylianou M,Levine SJ

doi

10.1016/j.rmed.2005.02.031

subject

Has Abstract

pub_date

2005-09-01 00:00:00

pages

1175-82

issue

9

eissn

0954-6111

issn

1532-3064

pii

S0954-6111(05)00066-1

journal_volume

99

pub_type

杂志文章,随机对照试验

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