Effects of intranasal TNFα on granulocyte recruitment and activity in healthy subjects and patients with allergic rhinitis

Henrik Widegren,Morgan Andersson,Jonas Erjefält,Magnus Korsgren,Lennart Greiff

doi:10.1186/1465-9921-9-15

Abstract

BackgroundTNFα may contribute to the pathophysiology of airway inflammation. For example, we have recently shown that nasal administration of TNFα produces late phase co-appearance of granulocyte and plasma exudation markers on the mucosal surface. The objective of the present study was to examine indices of granulocyte presence and activity in response to intranasal TNFα challenge.MethodsHealthy subjects and patients with allergic rhinitis (examined out of season) were subjected to nasal challenge with TNFα (10 μg) in a sham-controlled and crossover design. Nasal lavages were carried out prior to and 24 hours post challenge. Nasal biopsies were obtained post challenge. Nasal lavage fluid levels of myeloperoxidase (MPO) and eosinophil cationic protein (ECP) were analyzed as indices of neutrophil and eosinophil activity. Moreover, IL-8 and α2-macroglobulin were analyzed as markers of pro-inflammatory cytokine production and plasma exudation. Nasal biopsy numbers of neutrophils and eosinophils were monitored.ResultsNasal lavage fluid levels of MPO recorded 24 hours post TNFα challenge were increased in healthy subjects (p = 0.0081) and in patients with allergic rhinitis (p = 0.0081) (c.f. sham challenge). Similarly, α2-macroglobulin was increased in healthy subjects (p = 0.014) and in patients with allergic rhinitis (p = 0.0034). Lavage fluid levels of ECP and IL-8 were not affected by TNFα challenge. TNFα increased the numbers of subepithelial neutrophils (p = 0.0021), but not the numbers of eosinophils.ConclusionTNFα produces a nasal inflammatory response in humans that is characterised by late phase (i.e., 24 hours post challenge) neutrophil activity and plasma exudation.

Highlights

Tumour necrosis factor-α (TNFα) may contribute to the pathophysiology of airway inflammation
Nasal lavage fluid levels of MPO recorded 24 hrs post TNFα challenge were increased in healthy subjects (p = 0.0081) and in patients with allergic rhinitis (p = 0.0081) (c.f. sham challenge) (Fig. 1)
TNFα increased the numbers of subepithelial neutrophils in the study material as a whole (p = 0.0021) (Fig. 5): a subgroup analysis revealed that this change reflected a statistically significant increase in the healthy group (p = 0.0015), but not in the allergic rhinitis group (p = 0.204) (Fig. 6)

Summary

Introduction

TNFα may contribute to the pathophysiology of airway inflammation. For example, we have recently shown that nasal administration of TNFα produces late phase co-appearance of granulocyte and plasma exudation markers on the mucosal surface. Dysregulated TNFα responses are implicated in several inflammatory diseases including rheumatoid arthritis. In this condition, TNFα antagonism, either with recombinant (page number not for citation purposes). Inhalation of TNFα produces a response that is characterized by increased sputum numbers of granulocytes and increased airway responsiveness [9,10]. In refractory asthma, treatment with etanercept, an anti-TNFα measure, is associated with improvement in asthma symptoms, lung function, and airway hyperresponsiveness [11,12]. While these observations suggest an association between TNFα and bronchial airway inflammation, little is known about TNFα-induced nasal airway responses in man

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