In vitro experiments support the hypothesis that the Selleck Enzalutamide maximum influx of sCD14 might be around that time, because Landmann et al. have also shown a significant increase in sCD14 production in cell cultures 44 h after stimulation with LPS [44]. As expected, sCD14 concentrations differed markedly interindividually. While some subjects reacted with a large increase in sCD14 into the bronchoalveolar space at 18 and 42 h after allergen challenge, others had only minor increases. Whether this is owing to interindividual CD14 polymorphisms that have been shown to influence serum levels [45] or whether this merely reflects interindividual variability remains unclear. There was no correlation between sCD14 concentrations

and lung function or the type or dose of allergen used for challenge. Similarly, no correlation was found regarding sCD14 levels in BAL and IgE levels in blood (data not shown) as has been demonstrated by others [46]. sCD14 levels in BAL and in PBMC-CD14+ cultures learn more were lower than sCD14 measured in peripheral blood. This

could be because of a methodical influence of the BAL procedure where 100 ml of normal saline are used which dilute bronchoalveolar lining fluids, and the measured concentrations of sCD14 might therefore also be diluted. SCD14 levels in peripheral blood were in the range of sCD14 measured in other studies [47] but tended to be higher than those measured in cord and peripheral blood from allergic and non-allergic asthmatic children [30, 48]. Lundell et al. also found a trend for lower sCD14 levels in peripheral blood of children developing

allergies compared to healthy controls [48]. In our study, we also observed a slight trend towards lower sCD14 levels in allergic subjects compared to non-allergic controls (Figs. 2–4) but this did not reach statistical significance. The predominant isoform of sCD14 in BALF is the 49-kDa isoform, isometheptene which is produced intracellularly in mononuclear cells and secreted [28]. Therefore, sCD14 is produced locally in the bronchi. Recently, sCD14 has been discussed as an acute-phase protein, and sCD14 levels were correlated to CRP levels in patients with bacterial and non-bacterial inflammation [49]. Also, it is known that CRP and lipopolysaccharide-binding protein are elevated in peripheral blood serum after allergen challenge [28]. Therefore, it could be speculated that endobronchial sCD14 is also a parameter for asthmatic inflammation. To elucidate potential mechanisms that might contribute to sCD14 increase in allergic asthma, PBMC-CD14+ cultures were stimulated with LPS, LPS + LTD4, LTD4 and IL-17. IL-17 is a cytokine that mediates the LPS-induced accumulation of neutrophils in the respiratory tract [39], and incubation of PBMC-CD14+ cultures with IL-17 results in an increase in IL-6, IL-10, IL-12 and TNF-α production [50]. In our study, stimulation with IL-17 in vitro, however, had no effect on sCD14 levels in PBMC-CD14+ cultures.