[Mediators of immunologic inflammation of the respiratory tract]

The role of mediators in allergic inflammation of respiratory airways has recently been elucidated through the development of experimental systems for in vivo evaluation of hypersensitivity reactions in humans. Antigen challenge in hay-fever patients has been shown to be associated with the release of histamine, kinins, peptidoleukotrienes, leukotriene B4 and prostaglandin D2 in nasal secretions. Endobronchial antigen stimulation in asthmatic patients has been shown to induce local release of histamine, prostaglandin D2 and leukotriene C4. The effects of inflammatory mediators seem to be different: nasal challenge with histamine causes rhinorrhea, itching, sneezing and nasal obstruction, whereas local stimulation with leukotriene C4 and prostaglandin D2 induces only a marked obstruction. Bronchial provocation with histamine is associated with smooth muscle contraction, hypersecretion, vasodilation and increase in vascular permeability. Leukotriene C4 or prostaglandin D2 inhalation induces a marked bronchoconstriction. On molar basis, the potencies of these arachidonic acid derivatives are respectively about 1000 fold and 30 fold higher than that of histamine. Mast cells seem to play a pivotal role in the pathogenesis of immediate allergic responses, whereas eosinophils, neutrophils and basophils seem to be mainly involved in late phase reactions. Since paf-acether is a potent chemotactic factor for eosinophils and neutrophils, it is reasonable to suppose that this lipid mediator is generated during the immediate allergic reaction and is involved in the appearance of late phase responses.