Cytokine levels and inflammatory responses in developing late-phase allergic reactions in the skin

Background: Cytokines could play roles in the attraction of leukocytes into sites of IgE-mediated late-phase reactions (LPR) or in the activation of such cells at the sites, Previous studies found increased release of IL-6, IL-1, and granulocyte-macrophage colony-stimulating factor into skin chambers overlying allergen-challenged sites, mainly after 6 hours when LPR are already well-developed. Objective: To compare levels of several cytokines with inflammatory responses in skin chambers overlying developing LPRs. Methods: Skin chambers were appended to denuded blister bases in 15 sensitive subjects, then challenged over a 5-hour period with pollen allergens (Ag) or buffer control (B), Levels of several chemotactic cytokines, eosinophil cationic product (released from eosinophils), and lactoferrin (released from neutrophils) were measured and leukocyte accumulation was assessed. Results: Levels of the chemokines IL-8, RANTES, and monocyte chemotactic protein-1 (but not IL-1, IL-6, or granulocyte-macrophage colony-stimulating factor) were significantly higher at Ag-challenge sites than at B-challenge sites, IL-5 was not detected, In individual chamber fluids at Ag-challenge sites, (1) IL-8 levels correlated strongly with levels of lactoferrin but not with eosinophil cationic protein levels; (2) RANTES levels correlated with numbers of eosinophils hut not with eosinophil cationic protein levels; and (3) levels of monocyte chemotactic protein-1 correlated weakly with histamine released after the first hour. Conclusions: During LPRs developing during the first 5 hours of Ag challenge, there is increased local release of several chemokines, which could play roles in the observed attraction and subsequent activation of leukocytes and continued histamine release observed at such sites.