TY - JOUR
T1 - The pattern and kinetics in human skin of erythema and mediators during the acute and late-phase response (LPR)
AU - Reshef, Avner
AU - Kagey-Sobotka, Anne
AU - Adkinson, N. Franklin
AU - Lichtenstein, Lawrence M.
AU - Norman, Philip S.
N1 - Funding Information:
From the Department of Medicine, Division of Clinical Immunol-ogy, The Johns Hopkins University School of Medicine, Balti-more, Md. Supported by National Institutes of Health Grants AI 20136, AI 07056, AI 07290, and AI 08270, Bethesda, Md. Received for publicaton July 6, 1988. Revised April 3, 1989. Accepted for publication May 10, 1989. Reprint requests: Philip S. Norman, MD, Clinical Immunology Division, The Good Samaritan Hospital, 5601 Loch Raven Blvd., Baltimore MD 21239. Publication No. 767 from the O’Neill Laboratories at The Good Samaritan Hospital, Baltimore, Md. *Current address: Allergy and Clinical Immunology Service, The Rebecca Sieff Memorial Hospital, Safed 13100, Israel. **Recipient of a Pfizer Biomedical Research Award. l/1/14805
PY - 1989/11
Y1 - 1989/11
N2 - To investigate the kinetics and pattern of allergenically induced mediator release in the human skin, we have studied 24 ragweed- and grass-allergic patients with a blister-chamber technique. Chambers sealed to the skin around a denuded area, formed by unroofing a blister, were challenged with 0.5 ml of either diluent or 10 or 100 times the concentration of allergen required for 4+ early intradermal reaction. Chamber fluids were removed hourly 1 to 8 hours after antigen challenge and examined for the presence of histamine, leukotriene C4 (LTC4), and prostaglandin D2 to compare inflammatory mediator levels with the clinical early response and late-phase response (LPR), as assessed by erythema around the chamber. An initial erythema developed rapidly and began to subside after 1 hour in all patients, but a late-phase local erythema and subcutaneous swelling around the chamber (i.e., >2.5 cm, the outside diameter of the chamber) developed in 13/15 challenges only when the higher concentration of antigen was used. At both allergen concentrations, histamine levels peaked sharply at the first hour (20.6 ±2.3 ng/ml) and progressively declined during the next 4 hours by 75%, but remained above control levels for at least 7 hours. Despite high control values, LTC4 levels were significantly elevated (p < 0.01) 4 to 6 hours after challenge. In visible reactions, maximal LPR around the chamber correlated with LTC4 levels obtained 6 and 7 hours after challenge (p < 0.05). Prostaglandin D2 rose gradually in antigen-challenged chambers to a peak at 5 to 6 hours. Thus, early rises in histamine were temporally related to the immediate erythema, whereas the arachidonic acid metabolites from both cyclooxygenase and lipoxygenase pathways that appeared in the skin after allergen challenge followed kinetics that corresponded to the time course of cutaneous LPR.
AB - To investigate the kinetics and pattern of allergenically induced mediator release in the human skin, we have studied 24 ragweed- and grass-allergic patients with a blister-chamber technique. Chambers sealed to the skin around a denuded area, formed by unroofing a blister, were challenged with 0.5 ml of either diluent or 10 or 100 times the concentration of allergen required for 4+ early intradermal reaction. Chamber fluids were removed hourly 1 to 8 hours after antigen challenge and examined for the presence of histamine, leukotriene C4 (LTC4), and prostaglandin D2 to compare inflammatory mediator levels with the clinical early response and late-phase response (LPR), as assessed by erythema around the chamber. An initial erythema developed rapidly and began to subside after 1 hour in all patients, but a late-phase local erythema and subcutaneous swelling around the chamber (i.e., >2.5 cm, the outside diameter of the chamber) developed in 13/15 challenges only when the higher concentration of antigen was used. At both allergen concentrations, histamine levels peaked sharply at the first hour (20.6 ±2.3 ng/ml) and progressively declined during the next 4 hours by 75%, but remained above control levels for at least 7 hours. Despite high control values, LTC4 levels were significantly elevated (p < 0.01) 4 to 6 hours after challenge. In visible reactions, maximal LPR around the chamber correlated with LTC4 levels obtained 6 and 7 hours after challenge (p < 0.05). Prostaglandin D2 rose gradually in antigen-challenged chambers to a peak at 5 to 6 hours. Thus, early rises in histamine were temporally related to the immediate erythema, whereas the arachidonic acid metabolites from both cyclooxygenase and lipoxygenase pathways that appeared in the skin after allergen challenge followed kinetics that corresponded to the time course of cutaneous LPR.
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U2 - 10.1016/0091-6749(89)90296-0
DO - 10.1016/0091-6749(89)90296-0
M3 - Article
C2 - 2478604
AN - SCOPUS:0024404891
SN - 0091-6749
VL - 84
SP - 678
EP - 687
JO - The Journal of allergy and clinical immunology
JF - The Journal of allergy and clinical immunology
IS - 5 PART 1
ER -