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Using flow cytometric analysis technique and ovalbumin- (OVA-) sensitized mouse model, it was found that IL-18 and tryptase levels in the plasma of moderate and severe asthma were elevated, and they correlated well with each other. Tryptase and agonist peptides of protease activated receptor- (PAR-) 2 induced substantial quantity of IL-18 release. IL-18 and tryptase provoked mast cell accumulation in peritoneum of OVA-sensitized mice. OVA-sensitization increased number of IL-18 receptor (R)<jats:sup>+<\/jats:sup>mast cells. IL-18 and tryptase induced dramatic increase in IL-18R<jats:sup>+<\/jats:sup>mast cells and mean fluorescence intensity (MFI) of IL-18R on mast cells. Moreover, while IL-18 induced an increase in PAR-2<jats:sup>+<\/jats:sup>mast cells in nonsensitized mice, IL-18 and tryptase provoked increases in IL-4 and thymic stromal lymphopoietin (TSLP) in the peritoneum of OVA-sensitized mice. In summary, the correlation between IL-18 and tryptase in plasma of patients with asthma indicates close interactions between them, which should be considered for development of anti-IL-18 and antitryptase therapies. 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