This broad based project has explored various expressions of allergy over the past 17 years , ranging from anaphylaxis to asthma and rhinitis. One of the areas we have focused upon is the histamine releasing factor released from human neutrophils (HRA-N). HRA-N causes histamine release without concomitant arachidonic acid secretion, suggesting that unique pathways are involved. Corticosteroids are useful in the treatment of allergic diseases and one of the mechanisms by which it works was found to involve the ability of corticosteroids to inhibit HRA-N induced histamine release. This observation extends earlier work on the effects of corticosteroids on mast cell reactivity. Allergen challenge of the nasal mucosa in allergic individuals elicits an acute allergic reaction. We examined the effects of nedocromil on nasal provocation and found it to have no effect, suggesting that nedocromil may not be useful in the treatment of allergic rhinitis. The symptoms of allergic rhinitis are largely due to histamine-induced vascular permeability. We examined the distribution of histamine receptors in the nasal mucosa and found that H-1 receptors were localized to the vascular tissues exclusively. IL-4 is used in cancer chromotherapy but causes distressing nasal congestion, which often limits the use of IL-4. The congestion appears to be due to histamine release, perhaps due to increased susceptibility of nasal mast cells to HRA-N.
