Mortality in human sepsis is associated with downregulation of Toll-like receptor 2 and CD14 expression on blood monocytes

Pattern recognition receptors are a key component of the first line host defense against infection, recognizing specific microbial products. We hypothesize that monocyte hyporesponsiveness in human sepsis is associated with a downregulation of the pattern recognition receptors Toll-like receptor (TLR)-2 and TLR4

Hospital acquired pneumonia with high-risk bacteria is associated with increased pulmonary matrix metalloproteinase activity

Abstract Background Neutrophil products like matrix metalloproteinases (MMP), involved in bacterial defence mechanisms, possibly induce lung damage and are elevated locally during hospital- acquired pneumonia (HAP). In HAP the virulence of bacterial species is known to be different. The aim of this study was to investigate the influence of high-risk bacteria like S. aureus and pseudomonas species on pulmonary MMPconcentration in human pneumonia. Methods In 37 patients with HAP and 16 controls, MMP-8, MMP-9 and tissue inhibitors of MMP (TIMP) were analysed by ELISA and MMP-9 activity using zymography in bronchoalveolar lavage (BAL). Results MMP-9 activity in mini-BAL was increased in HAP patients versus controls (149 ± 41 vs. 34 ± 11, p Conclusion Pulmonary MMP concentrations and MMP activity are elevated in patients with HAP. This effect is most pronounced in patients with high-risk bacteria. Artificial ventilation may play an additional role in protease activation.</p

Cytokine secretion in human lung tissue and murine macrophages after challenge with nigericin, KCl, glibenclamide and NAC.

<p>A. Human lung tissue was stimulated either with nigericin 10 µM alone or together with NTHi 10⁶ cfu/ml. Sole challenge with nigericin did not lead to elevated IL-1β levels, whereas the addition of nigericin to NTHi primed macrophages enhanced the cytokine secretion; (n.s. = not significant). B. RAW cells were pretreated for 30 minutes with KCl 30 mM or glibenclamide 250 µM and then stimulated with NTHi 10⁶cfu/ml. IL-1β concentrations decreased significantly in both settings. C. RAW cells were preincubated with NAC 20 mM for 60minutes prior to stimulation with NTHi 10⁵ cfu/ml. IL-1β levels were reduced significantly in comparison to the control.</p

Cytokine secretion in murine macrophages after stimulation with non-viable NTHi.

<p>Murine macrophages were stimulated with inactivated NTHi for 24 h. IL-1β concentrations were significantly reduced compared to stimulation with viable NTHi (A). TNF-α and CXCL-2 levels were better preserved after stimulation with non-viable NTHi in comparison to IL-1β (B+C).</p