Effects of TNFalpha on the human nasal mucosa in vivo.
BACKGROUND
TNFalpha is a cytokine that may contribute to the pathophysiology of airway inflammation. Inhalation of TNFalpha produces granulocyte recruitment and airway hyperresponsiveness in man. Anti-TNFalpha treatment may inhibit allergen-induced plasma exudation in guinea-pig airways. Increased nasal mucosal output of TNFalpha has been demonstrated in allergic rhinitis, but the effect of TNFalpha on the human nasal mucosa has not been examined in vivo.


OBJECTIVE
To examine effects of topical TNFalpha on the human nasal mucosa in vivo.


METHODS
In a dose-finding study, healthy subjects received intranasal TNFalpha (0-7.5 microg). Nasal lavages were carried out before as well as 10 min and 24 h 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 TNFalpha (10 microg) was performed and followed 24 h later by an allergen challenge. Lavages were performed before the TNFalpha challenge, 24 h thereafter, and 10 min post allergen challenge. alpha(2)-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, TNFalpha produced significant increases in alpha(2)-macroglobulin 24h post challenge (p<0.01). In allergic rhinitis, 10 microg of TNFalpha also produced this effect (p<0.01) as well as increases in ECP and IL-8 (p<0.01). MPO was increased 24 h post challenge, but this change did not reach statistical significance. TNFalpha did not produce any acute effects and did not affect the responsiveness to allergen.


CONCLUSIONS
The present study demonstrates that topical TNFalpha produces a human nasal inflammatory response. These data suggest a role of TNFalpha in nasal conditions characterized by mucosal inflammation.
Widegren
Henrik
H
Department of Otorhinolaryngology, Head & Neck Surgery, Lund University Hospital, Lund, Sweden.
Korsgren
Magnus
M
Andersson
Morgan
M
Greiff
Lennart
L
D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D047150:Eosinophil Cationic Protein / Q000096:biosynthesis; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D016209:Interleukin-8 / Q000096:biosynthesis; D008297:Male; D017817:Nasal Lavage Fluid / Q000276:immunology; D009297:Nasal Mucosa / Q000187:drug effects* / Q000276:immunology; D009195:Peroxidase / Q000096:biosynthesis; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D000511:alpha-Macroglobulins / Q000096:biosynthesis
D000485:Allergens; D018836:Inflammation Mediators; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D000511:alpha-Macroglobulins; D009195:Peroxidase; D047150:Eosinophil Cationic Protein