Inhaled iloprost suppresses the cardinal features of asthma via inhibition of airway dendritic cell function
Marco Idzko, … , Henk C. Hoogsteden, Bart N. Lambrecht
Marco Idzko, … , Henk C. Hoogsteden, Bart N. Lambrecht
Published February 1, 2007
Citation Information: J Clin Invest. 2007;117(2):464-472. https://doi.org/10.1172/JCI28949.
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Research Article Immunology

Inhaled iloprost suppresses the cardinal features of asthma via inhibition of airway dendritic cell function

Abstract

Inhalation of iloprost, a stable prostacyclin (PGI2) analog, is a well-accepted and safe treatment for pulmonary arterial hypertension. Although iloprost mainly acts as a vasodilator by binding to the I prostanoid (IP) receptor, recent evidence suggests that signaling via this receptor also has antiinflammatory effects through unclear mechanisms. Here we show in a murine model of asthma that iloprost inhalation suppressed the cardinal features of asthma when given during the priming or challenge phase. As a mechanism of action, iloprost interfered with the function of lung myeloid DCs, critical antigen-presenting cells of the airways. Iloprost treatment inhibited the maturation and migration of lung DCs to the mediastinal LNs, thereby abolishing the induction of an allergen-specific Th2 response in these nodes. The effect of iloprost was DC autonomous, as iloprost-treated DCs no longer induced Th2 differentiation from naive T cells or boosted effector cytokine production in primed Th2 cells. These data should pave the way for a clinical effectiveness study using inhaled iloprost for the treatment of asthma.

Authors

Marco Idzko, Hamida Hammad, Menno van Nimwegen, Mirjam Kool, Nanda Vos, Henk C. Hoogsteden, Bart N. Lambrecht

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Figure 5

Iloprost treatment of DCs inhibits their potential to prime for Th2 responses.

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Iloprost treatment of DCs inhibits their potential to prime for Th2 resp...
(A and B) On day 0, mice received an i.t. injection of vehicle-treated OVA-pulsed DCs (vehicle-OVA-DC), iloprost-treated OVA-pulsed DCs, or unpulsed DCs. From days 10–13, all mice were exposed to OVA aerosols. (A) BAL fluid was analyzed by flow cytometry. (B) Hematoxylin and eosin staining of lung sections. (C) On day –2, mice were injected i.v. with OVA-specific naive T cells from DO11.10 mice. On day 0, mice were instilled i.t. with vehicle-treated OVA-pulsed DCs, iloprost-treated OVA-pulsed DCs, or unpulsed DCs. On day 4, LN cells were collected and cultured in 96-well plates for 4 days. (D) Supernatants of bone marrow–derived DCs treated overnight with vehicle or different concentrations of iloprost were collected. The presence of IL-4, IL-5, IL-10, IL-12, TNF-α, IL-13, and IFN-γ in the supernatants was analyzed by ELISA. Data are mean ± SEM. *P < 0.05; **P < 0.01; ***P < 0.001.