TY - JOUR T1 - Tiotropium reduced carbachol-induced axpressions of IL-6 and IL-8 by primary human lung fibroblasts of asthma and non-asthma subjects JF - European Respiratory Journal JO - Eur Respir J VL - 38 IS - Suppl 55 SP - p761 AU - Luigi Costa AU - Michael Roth AU - Paola Casarosa AU - Michael Tamm AU - Pieter Borger Y1 - 2011/09/01 UR - http://erj.ersjournals.com/content/38/Suppl_55/p761.abstract N2 - Asthma is a reversible, obstructive airway disease of unknown etiology. Although the molecular pathology of asthma is still obscure, muscarinic receptor antagonists are currently in use to treat the disease. Human lung fibroblasts express muscarinic receptors, which may regulate and fine-tune the expression of cytokine genes. In the present study we analyzed the effect of the muscarinic receptor agonist, carbachol, on the release of IL-8 and IL-6 by primary human lung fibroblasts obtained from asthmatic and non-asthmatic subjects. Fibroblasts were grown in RPMI-1640 (+10% FCS, 1% vitamins) in the presence of increasing carbachol concentrations (10-8M to 10-6M). Carbachol dose-dependently and significantly inhibited IL-6 release in IL-1β-stimulateded fibroblasts of non-asthmatics, but not in fibroblasts of asthma patients. Furthermore, Carbachol dose-dependently increased the IL-1β-induced IL-8 release, however, with no difference comparing fibroblasts obtained from asthmatics to cells of controls. The muscarinic receptor inhibitor tiotropium alone reduced the secretion of IL-6 and IL-8 by fibroblasts. Tiotropium (10-8 M) almost completely blocked the IL1beta-induced IL-6 and IL-8 secretion. Our data indicate that tiotropium reduces an inflammatory response of lung fibroblasts elicited by muscarinic receptors. These data may provide a rationale for the beneficial effects of tiotropium in the treatment of asthma.Supported by: Boehringer-Ingelheim Pharma and the Swiss National Foundation. ER -