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Effects of TNFalpha on the human nasal mucosa in vivo.

Widegren, Henrik LU ; Korsgren, Magnus LU ; Andersson, Morgan LU and Greiff, Lennart LU (2007) In Respiratory Medicine 101(9). p.1982-1987
Abstract
Background: TNF alpha is a cytokine that may contribute to the pathophysiology of airway inflammation. Inhalation of TNF alpha produces granulocyte recruitment and airway hyperresponsiveness in man. Anti-TNF alpha treatment may inhibit allergen-induced plasma exudation in guinea-pig airways. Increased nasal mucosal output of TNF alpha has been demonstrated in allergic rhinitis, but the effect of TNF alpha on the human nasal mucosa has not been examined in vivo. Objective: To examine effects of topical TNF alpha on the human nasal mucosa in vivo. Methods: In a dose-finding study, healthy subjects received intranasal TNFa (0-7.5 fig). Nasal lavages were carried out before as well as 10 min and 24h post challenge and alpha(2)-macroglobulin... (More)
Background: TNF alpha is a cytokine that may contribute to the pathophysiology of airway inflammation. Inhalation of TNF alpha produces granulocyte recruitment and airway hyperresponsiveness in man. Anti-TNF alpha treatment may inhibit allergen-induced plasma exudation in guinea-pig airways. Increased nasal mucosal output of TNF alpha has been demonstrated in allergic rhinitis, but the effect of TNF alpha on the human nasal mucosa has not been examined in vivo. Objective: To examine effects of topical TNF alpha on the human nasal mucosa in vivo. Methods: In a dose-finding study, healthy subjects received intranasal TNFa (0-7.5 fig). Nasal lavages were carried out before as well as 10 min and 24h post challenge and alpha(2)-macroglobulin was measured as an index of plasma exudation. In a second study, involving patients with allergic rhinitis examined out of season, a sham-controlled nasal challenge with TNF alpha (10 mu g) was performed and followed 24 h later by an allergen challenge. Lavages were performed before the TNF alpha challenge, 24h thereafter, and 10 min post allergen challenge. a2-Macroglobulin, eosinophil cationic protein (ECP), myeloperoxidase (MPO), and IL-8 were analyzed as indices of plasma exudation, eosinophil activity, neutrophil activity, and pro-inflammatory cytokine production, respectively. Results: In the dose-finding study, TNF alpha produced significant increases in alpha(2)-macroglobulin 24h post challenge (p < 0.01). In allergic rhinitis, 10 mu g of TNFa also produced this effect (p < 0.01) as well as increases in ECP and IL-8 (p < 0.01). MPO was increased 24h post challenge, but this change did not reach statistical significance. TNFcc did not produce any acute effects and did not affect the responsiveness to allergen. Conclusion: The present study demonstrates that topical TNFa produces a human nasal inflammatory response. These data suggest a role of TNF alpha in nasal conditions characterized by mucosal inflammation. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
exudation, IL-8, neutrophils, inflammation, eosinophils
in
Respiratory Medicine
volume
101
issue
9
pages
1982 - 1987
publisher
Elsevier
external identifiers
  • wos:000249092300018
  • scopus:34547483568
ISSN
1532-3064
DOI
10.1016/j.rmed.2007.04.005
language
English
LU publication?
yes
id
49751873-0f11-4852-b6e1-329681345cbd (old id 168041)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17532197&dopt=Abstract
date added to LUP
2007-07-06 11:16:38
date last changed
2017-01-01 07:14:01
@article{49751873-0f11-4852-b6e1-329681345cbd,
  abstract     = {Background: TNF alpha is a cytokine that may contribute to the pathophysiology of airway inflammation. Inhalation of TNF alpha produces granulocyte recruitment and airway hyperresponsiveness in man. Anti-TNF alpha treatment may inhibit allergen-induced plasma exudation in guinea-pig airways. Increased nasal mucosal output of TNF alpha has been demonstrated in allergic rhinitis, but the effect of TNF alpha on the human nasal mucosa has not been examined in vivo. Objective: To examine effects of topical TNF alpha on the human nasal mucosa in vivo. Methods: In a dose-finding study, healthy subjects received intranasal TNFa (0-7.5 fig). Nasal lavages were carried out before as well as 10 min and 24h post challenge and alpha(2)-macroglobulin was measured as an index of plasma exudation. In a second study, involving patients with allergic rhinitis examined out of season, a sham-controlled nasal challenge with TNF alpha (10 mu g) was performed and followed 24 h later by an allergen challenge. Lavages were performed before the TNF alpha challenge, 24h thereafter, and 10 min post allergen challenge. a2-Macroglobulin, eosinophil cationic protein (ECP), myeloperoxidase (MPO), and IL-8 were analyzed as indices of plasma exudation, eosinophil activity, neutrophil activity, and pro-inflammatory cytokine production, respectively. Results: In the dose-finding study, TNF alpha produced significant increases in alpha(2)-macroglobulin 24h post challenge (p &lt; 0.01). In allergic rhinitis, 10 mu g of TNFa also produced this effect (p &lt; 0.01) as well as increases in ECP and IL-8 (p &lt; 0.01). MPO was increased 24h post challenge, but this change did not reach statistical significance. TNFcc did not produce any acute effects and did not affect the responsiveness to allergen. Conclusion: The present study demonstrates that topical TNFa produces a human nasal inflammatory response. These data suggest a role of TNF alpha in nasal conditions characterized by mucosal inflammation.},
  author       = {Widegren, Henrik and Korsgren, Magnus and Andersson, Morgan and Greiff, Lennart},
  issn         = {1532-3064},
  keyword      = {exudation,IL-8,neutrophils,inflammation,eosinophils},
  language     = {eng},
  number       = {9},
  pages        = {1982--1987},
  publisher    = {Elsevier},
  series       = {Respiratory Medicine},
  title        = {Effects of TNFalpha on the human nasal mucosa in vivo.},
  url          = {http://dx.doi.org/10.1016/j.rmed.2007.04.005},
  volume       = {101},
  year         = {2007},
}