Inhaled iloprost suppresses the cardinal features of asthma via inhibition of airway dendritic cell function.
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.
Idzko
Marco
M
Department of Pulmonary Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
Hammad
Hamida
H
van Nimwegen
Menno
M
Kool
Mirjam
M
Vos
Nanda
N
Hoogsteden
Henk C
HC
Lambrecht
Bart N
BN
D000280:Administration, Inhalation; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006801:Humans; D016285:Iloprost / Q000008:administration & dosage*; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology / Q000473:pathology
D018927:Anti-Asthmatic Agents; D010047:Ovalbumin; D016285:Iloprost