Effects of TNFα on the human nasal mucosa in vivo

SummaryBackgroundTNFα is a cytokine that may contribute to the pathophysiology of airway inflammation. Inhalation of TNFα produces granulocyte recruitment and airway hyperresponsiveness in man. Anti-TNFα treatment may inhibit allergen-induced plasma exudation in guinea-pig airways. Increased nasal mucosal output of TNFα has been demonstrated in allergic rhinitis, but the effect of TNFα on the human nasal mucosa has not been examined in vivo.ObjectiveTo examine effects of topical TNFα on the human nasal mucosa in vivo.MethodsIn a dose-finding study, healthy subjects received intranasal TNFα (0–7.5μg). Nasal lavages were carried out before as well as 10min and 24h post challenge and α2-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 TNFα (10μg) was performed and followed 24h later by an allergen challenge. Lavages were performed before the TNFα challenge, 24h thereafter, and 10min post allergen challenge. α2-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.ResultsIn the dose-finding study, TNFα produced significant increases in α2-macroglobulin 24h post challenge (p<0.01). In allergic rhinitis, 10μg of TNFα also produced this effect (p<0.01) as well as increases in ECP and IL-8 (p