Pathogenesis and pharmacologic 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-phase reactions in these organs involve many mechanisms important in diseases such as atopic dermatitis, allergic rhinitis, and asthma. For this discussion, late-phase reaction research involving the skin model will be presented. Past research focused on the inflammatory components of late-phase reactions, but results were confounded by abrasion-related nonspecific inflammatory changes. Newer, less traumatic skin test methods have clarified the involvement of humoral and cellular elements 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, leukotriene C4, and tryptase. Dermal infiltrate abounds with eosinophils, basophils, neutrophils, and mononuclear cells several hours after challenge. Several investigators have shown that soluble proinflammatory cytokines are produced by cells at the antigen challenged site. Several of these cytokines may activate eosinophils and basophils, which release mediators of inflammation. Some of the newer nonsedating antihistamines appear to possess anti-inflammatory properties that may be unrelated to histamine antagonism and that might alter late inflammatory events of allergic disease.