CETP inhibition enhances monocyte activation and bacterial clearance and reduces streptococcus pneumonia-associated mortality in mice.

Sepsis is a leading cause of mortality worldwide, and pneumonia is the most common cause of sepsis in humans. Low levels of high-density lipoprotein cholesterol (HDL-C) levels are associated with an increased risk of death from sepsis, and increasing levels of HDL-C by inhibition of cholesteryl ester transfer protein (CETP) decreases mortality from intraabdominal polymicrobial sepsis in APOE*3-Leiden.CETP mice. Here, we show that treatment with the CETP inhibitor (CETPi) anacetrapib reduced mortality from Streptococcus pneumoniae-induced sepsis in APOE*3-Leiden.CETP and APOA1.CETP mice. Mechanistically, CETP inhibition reduced the host proinflammatory response via attenuation of proinflammatory cytokine transcription and release. This effect was dependent on the presence of HDL, leading to attenuation of immune-mediated organ damage. In addition, CETP inhibition promoted monocyte activation in the blood prior to the onset of sepsis, resulting in accelerated macrophage recruitment to the lung and liver. In vitro experiments demonstrated that CETP inhibition significantly promoted the activation of proinflammatory signaling in peripheral blood mononuclear cells and THP1 cells in the absence of HDL; this may represent a mechanism responsible for improved bacterial clearance during sepsis. These findings provide evidence that CETP inhibition represents a potential approach to reduce mortality from pneumosepsis.

Healthy orthorexia, orthorexia nervosa, and personality traits in a community sample in Turkey.

OBJECTIVE: Orthorexia nervosa is an eating disorder characterized by a rigid preoccupation with a perceived healthy diet. However, little is known about healthy orthorexia compared to orthorexia nervosa. The current study examined the relationship between healthy orthorexia and orthorexia nervosa and personality traits in a Turkish sample. METHODS: Three hundred fifty participants from a community sample aged 18-65 were included in the study. Participants completed a sociodemographic data collection form, Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Teruel Orthorexia Scale (TOS), and the 10-Item Personality Inventory (TIPI). RESULTS: The frequency of healthy orthorexia was 32.3% and orthorexia nervosa was 10.2%. There were no differences between genders regarding healthy orthorexia and orthorexia nervosa scores. Healthy orthorexia symptoms were negatively correlated with depression and anxiety (r = -0.11 and r = -0.20, respectively, P < .05), while they were positively correlated with agreeableness (r = 0.17), conscientiousness (r = 0.14), and extraversion (r = 0.15). Orthorexia nervosa symptoms were positively associated with anxiety (r = 0.12), depression (r = 0.10), and healthy orthorexia (r = 0.55). Hierarchical regression analyses demonstrated that depression was negatively associated with healthy orthorexia symptoms, explaining 4% of the variance. The agreeableness trait was positively associated with healthy orthorexia symptoms, explaining 4% of the variance. However, no specific personality trait was associated with orthorexia nervosa symptoms. CONCLUSION: To our knowledge, the present study is the first to examine the relationships between personality traits, healthy orthorexia, and orthorexia nervosa symptoms in a Turkish sample. Sociocultural factors may be important for understanding orthorexia nervosa and healthy eating behaviors in this population.