Effects of TNFalpha on the human nasal mucosa in vivo.

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)