IL-4 and IgE-anti-IgE modulation of 15(S)-hydroxyeicosatetraenoic acid release by mononuclear phagocytes

Background: IL-4 modulates the synthesis of IgE, the expression of CD23, an d the release of 15(S)-hydroxyeicosatetraenoic (15[S]-HETE). Objective: We evaluated the release of 15(S)-HETE by IL-4-stimulated monocy tes and verified whether the observed increase in 15(S)-HETE release after passive sensitization and anti-IgE challenge of IL-4-treated monocytes was secondary to an increased CD23 expression. Methods: Human monocytes were incubated for 24, 48, and 72 hours with IL-4 (10 ng/mL) with or without an Ige-anti-IgE stimulation. We evaluated CD23 e xpression by immunocytochemistry and 15(S)-HETE release by HPLC and RIA. To prove that the increase in 15(S)-HETE release was due to the effect of IL- 4 on CD23, we performed experiments with an anti-CDW blocking mAb. Results: CD23 expression and 15(S)-HETE release were significantly increase d by IL-4, reaching a peak after 72 hours (P < .02). After passive sensitiz ation with human IgE and anti-IgE challenge, IL-4-stimulated monocytes rele ased higher amounts of 15(S)-HETE than IL-4-unstimulated monocytes (P < .02 ). Pretreatment with the anti-human B-cell CD23 MHM6 mAb caused a dose-depe ndent inhibition of 15(S)-HETE release. Conclusions: This study shows that immunologic challenge of IL-4-treated, p assively sensitized monocytes results in a CD23-dependent additional increa se of 15(S)-HETE release, indicating the presence of a synergistic effect o f IL-4 on CD23 expression and 1`5(S)-HETE production.