Impact of Systemic Inflammation and Autoimmune Diseases on apoA-I and HDL Plasma Levels and Functions

The cholesterol of high-density lipoproteins (HDLs) and its major proteic component, apoA-I, have been widely investigated as potential predictors of acute cardiovascular (CV) events. In particular, HDL cholesterol levels were shown to be inversely and independently associated with the risk of acute CV diseases in different patient populations, including autoimmune and chronic inflammatory disorders. Some relevant and direct anti-inflammatory activities of HDL have been also recently identified targeting both immune and vascular cell subsets. These studies recently highlighted the improvement of HDL function (instead of circulating levels) as a promising treatment strategy to reduce inflammation and associated CV risk in several diseases, such as systemic lupus erythematosus and rheumatoid arthritis. In these diseases, anti-inflammatory treatments targeting HDL function might improve both disease activity and CV risk. In this narrative review, we will focus on the pathophysiological relevance of HDL and apoA-I levels/functions in different acute and chronic inflammatory pathophysiological conditions

Kinetics and pattern of viral excretion in biological specimens of two MERS-CoV cases

International audienc

Accuracy of leptin serum level in diagnosing ventilator-associated pneumonia: a case-control study

Background. Undernutrition causes a reduction of body-fat mass and a decrease in the circulating concentration of leptin which impairs the production of proinflammatory cytokines and increases the incidence of infectious diseases. The main objective of this study was to determine whether leptin deficiency is a risk factor for ventilator-associated pneumonia (VAP). Methods. This prospective observational case-control study was conducted in a university ICU during a 2-year period. Patients with VAP (cases) were matched (1:1) to patients without VAP (controls) according to all the following criteria: age, gender, SAPS II, and duration of ICU stay before VAP occurrence. In all patients leptin, C-reactive protein (CRP) and procalcitonin (PCT) were measured at ICU admission, and twice a week. In addition, in cases, leptin, CRP and PCT were also measured on the day of VAP diagnosis. Results. Eighty-six cases were matched with 86 controls. No significant difference was found in leptin and PCT levels between cases and controls. CRP level was significantly higher on the day of VAP in cases compared with controls (99 vs. 48 mg/L, P=0.001). Combination of CRP-leptin (CRP >= 78 mg/L and leptin >= 6.2 ng/mL on the day of VAP) was significantly (P=0.009) associated with VAP in univariate analysis. Multivariate analysis identified the combination of CRP-leptin (OR [95% CI] 3.08 [1.18-8.04], P=0.003), LOD score (1.27 [1.08-1.48], P=0.003), neuromuscular-blockers use (6.6 [2.03-21.7], P=0.002), and reintubation (3.3 [1.14-9.6], P=0.027) as independent risk factors for VAP. Conclusion. In our study, leptin level was not associated with VAP occurrence. Further studies are needed to confirm our results, and to define the exact inflammatory role of leptin, and its interest as a biomarker in ICU patients

Peroxisome proliferator-activated receptor gamma activation is required for maintenance of innate antimicrobial immunity in the colon

Crohn's disease (CD), a major form of human inflammatory bowel disease, is characterized by primary immunodeficiencies. The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) is essential for intestinal homeostasis in response to both dietary- and microbiota-derived signals. Its role in host defense remains unknown, however. We show that PPARγ functions as an antimicrobial factor by maintaining constitutive epithelial expression of a subset of β-defensin in the colon, which includes mDefB10 in mice and DEFB1 in humans. Colonic mucosa of Pparγ mutant animals shows defective killing of several major components of the intestinal microbiota, including Candida albicans, Bacteroides fragilis, Enterococcus faecalis, and Escherichia coli. Neutralization of the colicidal activity using an anti-mDefB10 blocking antibody was effective in a PPARγ-dependent manner. A functional promoter variant that is required for DEFB1 expression confers strong protection against Crohn's colitis and ileocolitis (odds ratio, 0.559; P = 0.018). Consistently, colonic involvement in CD is specifically linked to reduced expression of DEFB1 independent of inflammation. These findings support the development of PPARγ-targeting therapeutic and/or nutritional approaches to prevent colonic inflammation by restoring antimicrobial immunity in CD