Fatty acids as metabolic mediators in innate immunity.

BACKGROUND: Increasing data support the hypothesis of a local and systemic crosstalk between adipocytes and monocytes mediated by fatty acids. The aim of this study was to characterize the immunomodulatory effects of a large panel of fatty acids on cytokines and chemokines in monocytic THP-1 cells and primary human monocytes. We tested whether anti-inflammatory fatty acids are able to inhibit the binding of lipopolysaccharide (LPS) to its receptor, toll-like receptor/MD-2 (TLR4/MD-2). MATERIALS AND METHODS: Resistin, monocyte chemoattractant protein-1 (MCP-1) and tumour necrosis factor (TNF) were measured by enzyme-linked immunosorbent assay. Proteins were analysed by Western blot. A designed Flag-tagged TLR4/MD-2 fusion protein (LPS trap) was used to investigate the effect of fatty acids on binding of LPS to its receptor. In 30 patients with type 2 diabetes mellitus (T2D), the correlation of serum triglyceride levels with LPS-induced monocyte activation was analysed. RESULTS: Eleven fatty acids investigated exerted differential effects on the monocytic release of cytokines and chemokines. Eicosapentaenoic acid had potent anti-inflammatory effects on human primary monocytes and THP-1 cells; 100 and 200 microM eicosapentaenoic acid dose-dependently inhibited LPS binding to the LPS trap. LPS-induced release of monocytic MCP-1 and TNF was significantly and positively correlated with serum triglyceride levels in 30 patients with T2D. CONCLUSIONS: Monocytic activation is differentially regulated by fatty acids and depends on triglyceride levels in T2D. The main finding of the present study shows that eicosapentaenoic acid inhibits the specific binding of LPS to TLR4/MD-2. Eicosapentaenoic acid represents a new anti-inflammatory LPS-antagonist.

Adiponectin downregulates CD163 whose cellular and soluble forms are elevated in obesity.

BACKGROUND: CD163 is a monocyte/macrophage specific receptor whose soluble form (sCD163) is elevated in inflammatory diseases. Obesity is associated with chronic inflammation and low adiponectin, an anti-inflammatory adipokine. Adiponectin, 5-aminoimidazole-4-carboxamide-1-4-ribofuranoside (AICAR) and metformin activate the AMP-kinase that exerts anti-inflammatory effects, and the influence of adiponectin and these drugs on monocytic CD163 was analysed, and cellular and sCD163 were determined in obesity and type 2 diabetes. MATERIALS AND METHODS: Monocytes were incubated with adiponectin, AICAR or metformin. Furthermore, monocytes and serum were obtained from type 2 diabetic patients (T2D), overweight (defined as a body mass index > or = 25 kg m(-2)) and normal-weight (NW) controls. CD163 was analysed by immunoblot and sCD163 was measured by enzyme-linked immunosorbent assay in the supernatants of the monocytes and in serum. RESULTS: In monocytes, adiponectin reduced cellular and surface CD163, whereas sCD163 was not altered in the corresponding supernatants. Further, metformin and AICAR downregulated CD163. Monocytic CD163 was higher in T2D and obesity, whereas sCD163 in the supernatants was not elevated and neither correlated with serum sCD163 nor systemic adiponectin. There was a positive correlation of monocytic sCD163 with serum but not with monocytic IL-6. In the serum of obese controls and T2D patients, sCD163 was significantly higher compared to NW donors and was positively associated with systemic IL-6. CONCLUSIONS: This study indicates that monocytic CD163 and systemic sCD163 are elevated in T2D and obesity. Adiponectin reduces CD163 in vitro, but additional factors related to obesity like IL-6 may be more relevant in vivo.

Peritoneal fluid adipokines: ready for prime time?

BACKGROUND: Visceral adipose tissues secret a variety of adipokines; however, it is not known whether they are present in the peritoneal fluid. It was the aim of this study to investigate peritoneal fluid concentrations of novel (cartonectin, omentin) and classical adipokines (leptin, adiponectin, resistin, visfatin) in patients with ascites. MATERIAL AND METHODS: Ninety-six patients (71 men and 25 women) undergoing paracentesis were included. Of these, 76 suffered from liver cirrhosis. Adipokines were measured by enzyme-linked immunosorbent assay or Western blot. RESULTS: Each adipokine was detected in ascites with a broad range. Serum-ascites ratios (SAR) correlated with clinical and laboratory parameters. The main variables influencing peritoneal fluid adipokine concentrations were body mass index (BMI), local inflammation, systemic inflammation and serum adipokine concentrations. Resistin was significantly higher in patients with peritonitis and showed a positive correlation with peripheral leucocytes (white blood cell count). Leptin was correlated with the underlying disease. Visfatin correlated with peripheral white blood cell and C-reactive protein levels. Omentin expression was correlated with ascitic leucocyte count, ascitic albumin concentration and low albumin SAR. BMI was correlated positively with ascitic leptin levels and cartonectin protein levels. CONCLUSIONS: Peritoneal fluid adipokine concentrations are characterized by individual SARs, depend on the presence of peritonitis, and correlate with underlying disease, BMI and systemic inflammation. The data open a new field of research on the role of the peritoneum and visceral adipokines in gastrointestinal diseases.

Quantitative computed tomography of spine: comparison of three-dimensional and two-dimensional imaging approaches in clinical practice.

Quantitative computed tomography (QCT), a widely utilized technique for determining bone mineral density (BMD) at various skeletal sites, may yield less precise measurements if there are operator measurement errors and other technical variables. Two-dimensional (2D)and three-dimensional (3D)QCT scans of the lumbar spine of 21 women were compared in order to investigate the effects of potential operator variability on the precision of BMD measurements and to examine resulting differences of these imaging approaches in clinical practice. No significant difference was found (p > 0.05) in precision between the 2D and 3D QCT BMD measurements owing to operator measurement errors on the CT scans. The variability in BMD values within numerous small regions of interest (ROIs)( approximately 75 mm (2) ) of cancellous bone within a single vertebra was 10.1%, larger than the 2D or 3D BMD variability measured in typical regions ( approximately 250 mm (2)) by an order of magnitude. 3D BMD values in this population, which represented a wide range of clinical values, were found to be significantly greater than 2D BMD values by an average of 5.6% (p = 0.00024) relative to the 2D QCT values. Our findings suggest technical measurement error does not have a significant effect on precision of BMD measurements obtained with either QCT method. Several factors, however, including the incorporation of focal regions of higher density bone mass within the 3D QCT ROI may account for the higher BMD values compared with those for 2D QCT.

Corrosive substance ingestion: a review.

Patients who ingest caustic substances continue to pose difficult problems in diagnosis and management. Flexible endoscopy and radiological studies have helped to delineate the extent of damage caused by corrosives. Management techniques have been directed toward avoiding the development of esophageal strictures. Although a number of nonsurgical techniques are available, i.e., stenting, anticollagen agents, antibiotics, and corticosteroids none has been evaluated in well-controlled studies. In the future efforts should be made to evaluate adequately these management techniques. Public health efforts should be made to educate the public about the dangers of caustic substances so that their threat may be diminished.

The relation between obesity and testosterone-estradiol binding globulin levels in polycystic ovarian syndrome (PCO).

Serum testosterone-estradiol binding globulin levels (TEBG), total and free testosterone levels, were evaluated in 36 patients with polycystic ovarian syndrome (PCO), and nine volunteers with normal cycles. TEBG concentration was markedly reduced in all PCO patients in comparison to the controls. However, the difference between the means was statistically significant for the obese PCO patients only. The serum free testosterone levels were elevated in all PCO patients, although the total testosterone levels were normal in 42.8% of obese and 13.3% of nonobese patients. It is suggested that obesity is a factor in causing reduction of TEBG levels. Also, it might be a contributory factor in the etiology of PCO.