PATHOGENESIS AND PHARMACOLOGICAL MODULATION OF THE CUTANEOUS LATE-PHASE REACTION

Late-phase reactions that occur in response to local antigen challenge have been demonstrated in the skin, nose, and lungs of humans. Late-p hase reactions in these organs involve many mechanisms important in di seases such as atopic dermatitis, allergic rhinitis, and asthma. For t his discussion, late-phase reaction research involving the skin model will be presented. Past research focused on the inflammatory component s of late-phase reactions, but results were confounded by abrasion-rel ated nonspecific inflammatory changes. Newer, less traumatic skin test methods have clarified the involvement of humoral and cellular elemen ts in cutaneous late-phase reactions and demonstrated the efficacy of agents commonly used to treat allergenic conditions. Antigen challenge triggers the local release of histamine, prostaglandin D2, leukotrien e C4, and tryptase. Dermal infiltrate abounds with eosinophils, basoph ils, neutrophils, and mononuclear cells several hours after challenge. Several investigators have shown that soluble proinflammatory cytokin es are produced by cells at the antigen challenged site. Several of th ese cytokines may activate eosinophils and basophils, which release me diators of inflammation. Some of the newer nonsedating antihistamines appear to possess anti-inflammatory properties that may be unrelated t o histamine antagonism and that might alter late inflammatory events o f allergic disease.