30. 針刺麻酔に関する文献的ならびに基礎的研究(第519回千葉医学会例会 第8回佐藤外科例会)

<p>Cytokine response in lung homogenates, BALF and plasma of WT and <i>Trem-2</i>^<i>-/-</i> mice during experimental melioidosis.</p

TB associated cytokines after 4 and 6 weeks of infection.

<p>IL-17 (<b>A</b>) and IL-6 (<b>B</b>) are significantly increased in the infected mice (open symbols) compared with uninfected mice (black symbols) at 4 weeks after infection. At 6 weeks post infection levels in all infected and non-infected mice were similar and around the detection limit for both cytokines. IFNγ (<b>C</b>), IP-10 (<b>D</b>)and MIG (<b>E</b>) are increased both at 4 and 6 weeks after infection compared to non-infected mice. As MIG levels were higher in all infected mice than in all uninfected mice except 1, at 6 weeks significance was not reached (p = 0.08). Levels of MCP-1 (<b>F</b>) were increased in infected mice at 4 weeks post infection compared to uninfected mice. At both 4 and 6 weeks post infection the range of MCP-1 levels was quite wide between both infected and uninfected mice and levels at 6 weeks were very similar between infected and uninfected mice. * p<0.05, ** p<0.01, *** p<0.001</p

PLN activates HEK cells via TLR4.

<p>IL-8 production in HEK-293 cells transfected with CD14 and either TLR2 or TLR4 were incubated with medium (control), LPS (100 ng/ml), LTA (5 µg/ml) or PLN (1 µg/ml) for 6 hours. In some experiments polymyxin B (P) was used at 10 µg/ml. Data are mean±SEM (N = 4 per group). * P<0.01 versus control, † P<0.001 versus control, ‡P<0.001 versus LPS.</p

Cell composition in BALF of PBS-, LPS-, PLN- and heat inactivated PLN-treated mice.

<p>Macrophage and neutrophil counts in BALF from WT mice, 6 hours after inoculation of PBS, LPS (2 pg/mouse), heat inactivated PLN (HIPLN 500 ng/mouse) or PLN (500 ng/mouse). Data are plotted in Box&Whiskers graph (median+interquartile range N = 5 per group). * P<0.05 versus PBS.</p

Changes in cytokine levels during TB treatment.

<p>IFNγ, IP-10, MIG and MCP-1 levels were measured in infected (left hand panels, A, C, E, G) and non-infected (right hand panels, B, D, F, H) mice before (black squares) and after 3, 7, and 21 days of treatment with RIF+INH (open circles) or placebo (black circles). In the infected groups within 7–21 days of treatment with RIF+INH levels of all 4 cytokines were lower compared to placebo treated mice. In the non-infected mice no differences in levels were seen between different treatments or time points. * p<0.05, ** p<0.01, *** p<0.001</p

Inflammatory and cytolytic effects of PLN on mouse alveolar macrophage MH-S cells.

<p>MH-S cells were incubated with increasing doses of PLN for 6 hours with/without polymyxin B (10 µg/ml ) and TNF-α, MIP-2 and cell death were determined thereafter. Cell death was measured using MTT assay as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007993#s2" target="_blank">Methods</a> section. Data are mean±SEM (N = 5 per group). * P<0.05, † P<0.01 versus control.</p

Roles of TLR2 and TLR4 in lung inflammatory response to high dose PLN <i>in vivo</i>.

<p>Macrophage and neutrophil counts, total protein, IL-6, IL-1β, TNF-α and KC concentrations in BALF from WT, TLR2 KO and TLR4 KO mice, 6 hours after inoculation of 500 ng/mouse. Data are plotted in Box&Whiskers graph (median+interquartile range N = 8 per group). * P<0.05, † P<0.01, ‡ P<0.001 versus WT mice. Dotted line indicates mean value of PBS-treated mice.</p

Lung CFU and relative lung weights of mice.

<p><b>A</b>: Relative lung weights were calculated as a percentage of total body mass (mean +− SE). Black squares: uninfected placebo, open squares: uninfected RIF+INH treated, black circles: infected placebo, open circles: infected RIF+INH treated mice. At start of treatment, relative lung weights were increased in infected mice compared to uninfected mice (p<0.001). After an initial increase within 3 days, relative lung weight started to decrease within 3–7 days after start of treatment with RIF+INH in the infected mice although remaining higher than in the uninfected mice until the end of the experiment (p<0.01). Treatment had no effect on lung weight in uninfected mice. <b>B</b>: CFU counts of lung homogenates of sacrificed mice. Median baseline level in infected mice prior to treatment was 1.3×10⁶CFU per lung (black squares) and similar levels were found after 7 and 21 days of placebo treatment (black circles, 3 days not available due to contamination of culture plates). Treatment with RIF+INH strongly reduced CFU counts within 7 days (open circles; detection limit 2×10³ CFU/lung). Counts from 1 mouse are not available due to contamination. Cultures of undiluted lung homogenates from uninfected mice yielded no TB colonies (not shown). ** p<0.01</p

sCD14 exerts bimodal effects in acute lung inflammation depending on the dose of S-LPS.

<p>WT and CD14KO mice were treated intranasally with 10 µg S-LPS (left panel) or 0.1 µg S-LPS (right panel) and 10 µg sCD14 was administered simultaneously with S-LPS to groups of CD14KO mice. Six hours after LPS (and sCD14) administration, BALF was isolated and analyzed for PMN counts (A, B), TNF levels (C, D) and LIX levels (ER, F). Eight to nine mice were used per group. Data are are mean ± SEM. *, P<0.05; **, P<0.01; ***, P<0001 versus WT mice; ##, P<0.01; ###, P<0.001 versus CD14KO mice.</p

Pulmonary CD14 partially diminishes lung inflammation by high dose R-LPS, but enhances lung inflammation by low dose R-LPS.

<p>Mice (n = 6–9) were treated intranasally with 10 µg R-LPS (left panel), 1 µg R-LPS (middle panel) or 0.1 µg R-LPS (right panel). Six hours after LPS administration, BALF was isolated and analysed for PMN counts (A–C), TNF levels (D–F) and LIX levels (G–I). Data are mean ± SEM. *, P<0.05; **, P<0.01; ***, P<0001 versus WT mice.</p