Original Paper Int Arch Allergy Immunol 2002;129:254–260 DOI: 10.1159/000066772 Secretion of Cytokines, Histamine and Leukotrienes in Chronic Urticaria Marta Ferrer a Esther Luquin a Alfonso Sanchez-Ibarrola b Cristina Moreno b Maria L. Sanz a Allen P. Kaplan c a Department of Allergy and Clinical Immunology and b Department of Immunology, Clı ´nica Universitaria, Universidad de Navarra, Pamplona, Spain; c The Konishi-MUSC Institute for Inflammation Research, Department of Medicine, Division of Pulmonary and Critical Care and Allergy and Clinical Immunology, Medical University of South Carolina, Charleston, S.C., USA Received: February 6, 2002 Accepted after revision: July 9, 2002 Correspondence to: Dr. Marta Ferrer Departamento de Alergologı ´a Clinical Universitaria, Universidad de Navarra, Aptdo 4209 E–31008 Pamplona (Spain) Tel. +34 94 8296487, Fax +34 94 8296500, E-Mail mferrerp@unav.es ABC Fax + 41 61 306 12 34 E-Mail karger@karger.ch www.karger.com © 2002 S. Karger AG, Basel 1018–2438/02/1293–0254$18.50/0 Accessible online at: www.karger.com/iaa Key Words Basophil W Cytokines W Histamine W IL-4 W Urticaria W Mast cell W Leukotriene Abstract Background: Approximately 35–40% of patients with chronic urticaria have an IgG autoantibody to the IgE receptor which can activate basophils and mast cells so that they release histamine. In this study we assessed the cytokine profile present in chronic urticaria sera, and then measured cytokine and leukotriene release from basophils and mast cells upon incubation with chronic urticaria sera. Finally we assessed cytokine expression at the single-cell level and characterized the T cell subpopu- lations involved in their production. We chose IL-4 as representative of Th2 lymphocytes and IFN-Á for Th1 lymphocytes. M ethods: We analyzed IL-4, IL-5 and IFN-Á in 60 chronic urticaria sera versus 51 controls. Sera were incubated with purified human basophils and cutaneous mast cells and the release of histamine, IL-4 and leuko- trienes (C 4 , D 4 , E 4 ) was quantitated. Immunoblotting was performed to identify IgG antibody to FcÂRI·, · subunit. We measured intracellular cytokine production in pe- ripheral blood mononuclear cells of 17 chronic urticaria patients compared to 50 healthy controls. Results: We found higher IL-4 levels (p = 0.028) in the sera of chronic urticaria patients (1.03 pg/ml) versus healthy donors (0.20 pg/ml) but no difference between urticaria sera and atopic control sera (0.52 pg/ml). We did not detect IFN-Á or IL-5 in any serum. However, sera that activated baso- phils so that they released histamine also produced leu- kotriene and IL-4, and leukotriene production by cuta- neous mast cells and basophils was closely correlated. However, there was no correlation between immuno- blotting and the functional ability to induce either hista- mine or IL-4. After stimulating with PMA-ionomycin we found significant differences in CD4+ lymphocyte pro- duction of IL-4 and IFN-Á with no differences in CD8+ lymphocyte production of either cytokine. Conclusion: Our data support the presence of basophil and mast cell activators in the sera of patients with chronic urticaria which can lead to the production of leukotrienes and IL-4 in addition to the histamine. IL-4 levels are similar to those seen in atopic subjects. We found that CD4+ T cells from patients with chronic urticaria are activated and tend to produce higher cytokine levels than CD4+ T cells from healthy controls. There were no differences when cytokine production by CD8+ lymphocytes was similarly assessed. These results are consistent with the histology found in biopsies of chronic urticaria lesions, where a CD4+-predominant infiltrate is found with cytokine pro- duction suggesting either a Th0 response or a mixture of Th1 and Th2 lymphocytes. Copyright © 2002 S. Karger AG, Basel