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 2

Effect of iloprost treatment on distribution of DCs.

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Effect of iloprost treatment on distribution of DCs. Single-cell suspens...
Single-cell suspensions from MLNs were stained for DCs (A) or B and T cells (B) and analyzed by flow cytometry. Experiments were set up as in Figure 1. Labels indicate sensitization/treatment/challenge. Data (mean ± SEM) were calculated as absolute number of cells. **P < 0.01; ***P < 0.001. (C) Iloprost inhibited the maturation of lung DCs in vivo. A single-cell suspension was prepared from the lungs, and CD11c+MHCIIhi lung DCs were analyzed for their expression of CD40, CD80, CD83, and CD86. Data from 1 representative experiment of 3 is shown.