TNF-ALPHA IS LOCALIZED TO NASAL MUCOSAL MAST-CELLS AND IS RELEASED IN ACUTE ALLERGIC RHINITIS

Allergic mucosal inflammation is characterized by tissue infiltration with eosinophils, and associated activation of mast cells and T lymphocytes. Tumour necrosis factor (TNF) alpha/cachectin is a candidate cytokine relevant to the pathogenesis of these events through its capacity to upregulate the expression of endothelial cell adhesion molecules, mediate granulocyte chemoattraction, and activate eosinophils, mast cells and T cells. To investigate the presence and localization of TNF alpha in the nasal mucosa in allergic rhinitis, nasal biopsies from perennial rhinitic (n=13) and non-rhinitic volunteers (n=11) were embedded in glycol methacrylate and immunostained with a monoclonal antibody directed against TNF alpha, and adjacent 2 mu m sections stained for tryptase, CD3 and eosinophil cationic protein. This identified positive immunostaining for TNF alpha in the submucosa of both the rhinitic and normal subjects (median cell counts 13 and 23 cells/mm(2) respectively, P=0.24) with cellular localization to mast cells but not to T-lymphocytes or eosinophils. In a subsequent study of seven atopic subjects, nasal allergen challenge produced increases in lavage levels of histamine and albumin, which was associated with significant release of TNF alpha as early as 2 min post-allergen when compared with the saline control day (P=0.05). This difference was also apparent when studying the area under the curve both at 30 and 60 min postchallenge t-test (P=0.015 and 0.02 respectively). These findings which both locate immunoreactive TNF alpha to nasal mast cells and identify its release following in vivo exposure to allergen, provide evidence for mast cells as an important source of this cytokine in patients with allergic rhinitis.