Effects of intranasal TNFalpha on granulocyte recruitment and activity in healthy subjects and patients with allergic rhinitis.
BACKGROUND
TNFalpha may contribute to the pathophysiology of airway inflammation. For example, we have recently shown that nasal administration of TNFalpha 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 TNFalpha challenge.


METHODS
Healthy subjects and patients with allergic rhinitis (examined out of season) were subjected to nasal challenge with TNFalpha (10 microg) 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 alpha2-macroglobulin were analyzed as markers of pro-inflammatory cytokine production and plasma exudation. Nasal biopsy numbers of neutrophils and eosinophils were monitored.


RESULTS
Nasal lavage fluid levels of MPO recorded 24 hours post TNFalpha challenge were increased in healthy subjects (p = 0.0081) and in patients with allergic rhinitis (p = 0.0081) (c.f. sham challenge). Similarly, alpha2-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 TNFalpha challenge. TNFalpha increased the numbers of subepithelial neutrophils (p = 0.0021), but not the numbers of eosinophils.


CONCLUSIONS
TNFalpha produces a nasal inflammatory response in humans that is characterised by late phase (i.e., 24 hours post challenge) neutrophil activity and plasma exudation.
Widegren
Henrik
H
Department of Otorhinolaryngology, Head & Neck Surgery, Lund University Hospital, Lund, Sweden. henrik.widegren@skane.se
Erjefält
Jonas
J
Korsgren
Magnus
M
Andersson
Morgan
M
Greiff
Lennart
L
D000281:Administration, Intranasal; D000328:Adult; D001706:Biopsy; D018592:Cross-Over Studies; D047150:Eosinophil Cationic Protein / Q000378:metabolism; D004804:Eosinophils / Q000378:metabolism / Q000473:pathology; D005260:Female; D006098:Granulocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D017817:Nasal Lavage Fluid / Q000166:cytology; D009297:Nasal Mucosa / Q000378:metabolism / Q000473:pathology; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D011014:Pneumonia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006255:Rhinitis, Allergic, Seasonal / Q000378:metabolism* / Q000473:pathology*; D016037:Single-Blind Method; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology*; D000511:alpha-Macroglobulins / Q000378:metabolism
D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D000511:alpha-Macroglobulins; D009195:Peroxidase; D047150:Eosinophil Cationic Protein; C479220:RNASE3 protein, human