A) BAY 73-4506 in vitro Representative micrographs of Hematoxylin- and Eosin-stained lung sections from mice 42 h after infection. Note that the high statin fed mice exhibit reduced cellularity and vascular hemorrhage. Original magnification, 10X. B) Vascular integrity was determined by assessing the amount of albumin present in the BAL fluid by ELISA prior to and following infection (n = 3/group for uninfected and n = 6/group for infected mice). Data are presented as the mean ± SEM. Statistics were determined by a two-tailed student’s t-test. P < 0.05 was considered significant in comparison to Control fed mice. We subsequently
examined the impact of oral simvastatin therapy Selleckchem GSK1210151A on development of bacteremia. Following intratracheal challenge at 24 hpi, bacterial titers in the blood were not significantly different among all three groups tested; although mice receiving HSD had lower median titers compared to mice on the control diet (P = 0.12) (Figure 3). Between 24 and 36 h, pneumococcal titers in the blood increased at a similar rate for all {Selleck Anti-diabetic Compound Library|Selleck Antidiabetic Compound Library|Selleck Anti-diabetic Compound Library|Selleck Antidiabetic Compound Library|Selleckchem Anti-diabetic Compound Library|Selleckchem Antidiabetic Compound Library|Selleckchem Anti-diabetic Compound Library|Selleckchem Antidiabetic Compound Library|Anti-diabetic Compound Library|Antidiabetic Compound Library|Anti-diabetic Compound Library|Antidiabetic Compound Library|Anti-diabetic Compound Library|Antidiabetic Compound Library|Anti-diabetic Compound Library|Antidiabetic Compound Library|Anti-diabetic Compound Library|Antidiabetic Compound Library|Anti-diabetic Compound Library|Antidiabetic Compound Library|Anti-diabetic Compound Library|Antidiabetic Compound Library|Anti-diabetic Compound Library|Antidiabetic Compound Library|Anti-diabetic Compound Library|Antidiabetic Compound Library|buy Anti-diabetic Compound Library|Anti-diabetic Compound Library ic50|Anti-diabetic Compound Library price|Anti-diabetic Compound Library cost|Anti-diabetic Compound Library solubility dmso|Anti-diabetic Compound Library purchase|Anti-diabetic Compound Library manufacturer|Anti-diabetic Compound Library research buy|Anti-diabetic Compound Library order|Anti-diabetic Compound Library mouse|Anti-diabetic Compound Library chemical structure|Anti-diabetic Compound Library mw|Anti-diabetic Compound Library molecular weight|Anti-diabetic Compound Library datasheet|Anti-diabetic Compound Library supplier|Anti-diabetic Compound Library in vitro|Anti-diabetic Compound Library cell line|Anti-diabetic Compound Library concentration|Anti-diabetic Compound Library nmr|Anti-diabetic Compound Library in vivo|Anti-diabetic Compound Library clinical trial|Anti-diabetic Compound Library cell assay|Anti-diabetic Compound Library screening|Anti-diabetic Compound Library high throughput|buy Antidiabetic Compound Library|Antidiabetic Compound Library ic50|Antidiabetic Compound Library price|Antidiabetic Compound Library cost|Antidiabetic Compound Library solubility dmso|Antidiabetic Compound Library purchase|Antidiabetic Compound Library manufacturer|Antidiabetic Compound Library research buy|Antidiabetic Compound Library order|Antidiabetic Compound Library chemical structure|Antidiabetic Compound Library datasheet|Antidiabetic Compound Library supplier|Antidiabetic Compound Library in vitro|Antidiabetic Compound Library cell line|Antidiabetic Compound Library concentration|Antidiabetic Compound Library clinical trial|Antidiabetic Compound Library cell assay|Antidiabetic Compound Library screening|Antidiabetic Compound Library high throughput|Anti-diabetic Compound high throughput screening| mice, nonetheless mice on HSD had significantly fewer pneumococci in their blood compared to control mice (P = 0.007). After
36 h, mice receiving the control diet continued to experience bacterial replication whereas those on a simvastatin diet maintained or began to clear bacteria from the blood. At 42 hpi, mice on the HSD continued to have significantly less bacterial titers in the blood compared to control fed mice (P = 0.03). Figure 3 Mice on simvastatin prophylaxis show enhanced protection from bacteremia. Bacterial titers in the blood of challenged mice 24, 36 and 42 h after infection. Mice on Control (n = 11), Low (n = 11) or High (n = 12) diet were challenged intratracheally with 1 X 105 cfu. Mice receiving statins
had significantly fewer bacteria in the blood. Data are presented as the mean ± SEM. Statistics were determined by a two-tailed student’s t-test. P < 0.05 was considered significant. High-dose simvastatin reduces chemokine production in the lungs Statins have been reported to reduce cytokine Diflunisal production following LPS stimulation of monocytes and decrease lung inflammation following instillation of LPS in healthy human volunteers [18, 19]. Thus we investigated the effect of simvastatin therapy on the local and systemic production of cytokines and chemokines during pneumococcal pneumonia. At 24 hpi, before bacterial titers in the lungs were significantly different, no differences were observed for TNFα, IL-6, IL-10, IL-12, MCP-1, KC and IFNγ in the BAL fluid or serum of mice on LSD versus controls (Figure 4A, B). In contrast, mice on HSD had significant reductions in MCP-1 (P = 0.03) and KC (P = 0.02) in the BAL fluid but not serum. No differences were observed for all other cytokines or chemokines in the BALF or in the serum of HSD mice.