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, and the release of 15(S)-hydroxyeicosatetraenoic (15[S]-HETE). Objective: We evaluated the release of 15(S)-HETE by IL4-stimulated monocytes 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 expression 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-CD23 blocking mAb. Results: CD23 expression and 15(S)-HETE release were significantly increased by IL-4, reaching a peak after 72 hours (P < .02). After passive sensitization with human IgE and anti-IgE challenge, IL- 4-stimulated monocytes released 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-dependent inhibition of 15(S)-HETE release. Conclusions: This study shows that immunologic challenge of IL-4-treated, passively sensitized monocytes results in a CD23-dependent additional increase of 15(S)-HETE release, indicating the presence of a synergistic effect of IL-4 on CD23 expression and 15(S)-HETE production.