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

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

Department of Pulmonary Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.

The Journal of clinical investigation 2007 Feb

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Inhalation of iloprost, a stable prostacyclin (PGI(2)) 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.

Citation

Marco Idzko, Hamida Hammad, Menno van Nimwegen, Mirjam Kool, Nanda Vos, Henk C Hoogsteden, Bart N Lambrecht. Inhaled iloprost suppresses the cardinal features of asthma via inhibition of airway dendritic cell function. The Journal of clinical investigation. 2007 Feb;117(2):464-72