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

Allergic mucosal inflammation is characterized by tissue infiltration with eosinophils, and associated activation of mast cells and T lympho cytes. Tumour necrosis factor (TNF) alpha/cachectin is a candidate cyt okine relevant to the pathogenesis of these events through its capacit y to upregulate the expression of endothelial cell adhesion molecules, mediate granulocyte chemoattraction, and activate eosinophils, mast c ells and T cells. To investigate the presence and localization of TNF alpha in the nasal mucosa in allergic rhinitis, nasal biopsies from pe rennial rhinitic (n=13) and non-rhinitic volunteers (n=11) were embedd ed 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 positiv e immunostaining for TNF alpha in the submucosa of both the rhinitic a nd normal subjects (median cell counts 13 and 23 cells/mm(2) respectiv ely, P=0.24) with cellular localization to mast cells but not to T-lym phocytes or eosinophils. In a subsequent study of seven atopic subject s, nasal allergen challenge produced increases in lavage levels of his tamine and albumin, which was associated with significant release of T NF 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 immun oreactive TNF alpha to nasal mast cells and identify its release follo wing in vivo exposure to allergen, provide evidence for mast cells as an important source of this cytokine in patients with allergic rhiniti s.