Long-term exacerbation by interleukin 13 of IgE-mediated eosinophilia in rats

• Published in: International immunopharmacology Vol. 5; no. 9; pp. 1353 - 1364
• Main Authors: Rossi, Maria Inês Doria, de Oliveira Barreto, Emiliano, Pires, Ana Lúcia Aguiar, Rossi, Maria Isabel Doria, Dias, Vanessa Aparecida Ribeiro, Cordeiro, Renato Sérgio Balão, Martins, Marco Aurélio, Lima, Marcia Coronha Ramos
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.08.2005; Elsevier
• Subjects: Animals; Biological and medical sciences; Cell Movement; Chemokine CCL11; Chemokines, CC - biosynthesis; Eosinophil infiltration; Eosinophilia - immunology; Eosinophils - immunology; Hypersensitivity, Immediate - immunology; IgE-dependent allergy; IL-13 priming; Immunoglobulin E - immunology; Interleukin-13 - biosynthesis; Interleukin-13 - toxicity; Leukotriene C4 - biosynthesis; Lipoxygenase Inhibitors; Mast cells; Mast Cells - cytology; Mast Cells - immunology; Medical sciences; Pharmacology. Drug treatments; Rats; Rats, Wistar; IL-13 priming; Mast cells; Eosinophil infiltration; IgE-dependent allergy; Immunopathology; Allergy; Rat; IgE; Cytokine; Rodentia; Granulocyte; Priming; Hemopathy; Interleukin 13; Eosinophilia; Long term; Eosinophil; Exacerbation; Vertebrata; Mammalia; Animal; Infiltration; Mast cell
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2005.02.014

Recent work shows that at least two cycles of antigen challenge applied in a 7-day interval are required to yield tissue eosinophil accumulation in IgE-passively sensitized rats. Since interleukin (IL)-13 is widely regarded as a key mediator in eosinophilic responses associated with mast cells and IgE, we investigated whether this cytokine could replace the first cycle of sensitization and challenge in its proeosinophilic role. We found that IL-13 (25 and 50 ng/cavity) injected into the rat pleural space led to eotaxin generation and a dose-dependent accumulation of eosinophils following IgE-passive sensitization and challenge 7 days later. IL-13 failed to cause eosinophil chemotaxis in vitro but induced eosinophil accumulation into the pleural cavity of naïve rats, which peaked 1 day and faded 72 h post-challenge. No changes were found 1 week after intrapleural injection of IL-13, except a ∼ 40–50% increase in the number of adhered and non-adhered pleural mast cells. As recovered from the pleural effluent 1 week after IL-13, mast cells expressed the same amount of IgE bound on their surface as compared to controls. However, they generated 3-fold more LTC 4 following IgE-sensitization and challenge in vitro, keeping intact the amount of histamine released. Finally, pretreatment with zileuton (50 μg/cavity) 1 h before allergen challenge prevented eosinophil accumulation in those animals injected with IL-13 1 week before. In conclusion, our findings show that IL-13 causes a long-term exacerbation of the IgE-mediated eosinophilic response in a mechanism associated with heightened cysteinyl–leukotriene (cys–LT) production by resident mast cells.