Abstract
Rationale The role and contribution of eosinophils to allergic inflammation is under re-evaluation and may include activities that regulate lymphocyte function. For example, recent studies in mice suggest that IL-18 regulates polarization of Th1 and Th2 lymphocytes and results in generation of IL-4 and IL-13 to cause airway dysfunction. We sought to determine whether human eosinophils are capable of producing IL-18 and thus participate in regulation of Th1 or Th2 lymphocytes. Methods Human peripheral blood eosinophils and bronchoalveolar lavage (BAL) eosinophils (obtained 24 hours post segmental antigen challenge) were isolated and then assayed for the expression of IL-18 mRNA and secreted IL-18 protein by quantitative real-time PCR and ELISA assays, respectively. Results Isolated peripheral blood eosinophils that were cultured for up to 24 hours were found to secrete IL-18, which was not modulated by IL-5 treatment. Quantitative real time PCR revealed that eosinophils purified from BAL also express IL-18 mRNA. ELISA analysis of the corresponding BAL fluid detected IL-18 protein with a mean concentration of 84 pg/mL in atopic individuals and 48 pg/mL in nonatopic controls. Conclusions We demonstrated that human eosinophils can express IL-18 mRNA and secrete IL-18 protein. Given that the precise role for eosinophils in the asthmatic lung airway is unclear, we propose that eosinophil secretion of cytokines, such as IL-18, may play a regulatory role in airway inflammation by modulation of Th1 or Th2 lymphocytes.
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