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 1

Local administration of iloprost suppresses asthma features.

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Local administration of iloprost suppresses asthma features. Mice were s...
Mice were sensitized by i.p. injection of OVA/alum (see Methods) on days 0 and 7 and were exposed on days 19–21 to OVA aerosols. Prior to each aerosol, mice received an i.t. injection of vehicle, CAY10449 plus vehicle (OVA/CAY+vehicle/OVA), 0.2 μg iloprost, or CAY10449 plus iloprost. Labels indicate sensitization/treatment/challenge. (A and D) BAL fluid was analyzed by flow cytometry. (B) May-Grunwald-Giemsa staining of lung sections. (C and E) Cytokine production in MLN cells restimulated in vitro for 4 days with OVA. (F) BHR to various doses of i.v. metacholine was assessed for changes in dynamic resistance and lung compliance and BHR to inhaled metacholine for PenH responses was assessed 24 hours after the last antigen exposure were measured. Data are mean ± SEM; n = 8 mice per group. *P < 0.05; **P < 0.01; ***P < 0.001.