K. Carpenter, Jillian L. Ewing, Jane M. Schuh
Aug 1, 2005
Citations
1
Influential Citations
22
Citations
Quality indicators
Journal
British Journal of Pharmacology
Abstract
1 CC chemokine receptor 1 (CCR1) represents a promising target in chronic airway inflammation and remodeling due to fungus‐associated allergic asthma. 2 The present study addressed the therapeutic effect of a nonpeptide CCR1 antagonist, BX‐471, in a model of chronic fungal asthma induced by Aspergillus fumigatus conidia. 3 BX‐471 treatment of isolated macrophages inhibited CCL22 and TNF‐α and promoted IL‐10 release. BX‐471 also increased toll like receptor‐9 (TLR9) and decreased TLR2 and TLR6 expression in these cells. 4 When administered daily by intraperitoneal injection, from days 15 to 30 after the initiation of chronic fungal asthma, BX‐471 (3, 10, or 30 mg kg−1) dose‐dependently reduced airway inflammation, hyper‐responsiveness, and remodeling at day 30 after conidia challenge. The maximal therapeutic effect was observed at the 10 mg kg−1 dose. 5 In summary, the therapeutic administration of BX‐471 significantly attenuated experimental fungal asthma via its effects on both innate and adaptive immune processes.