Inflammation may modulate IL-6 and C-reactive protein gene expression in the adipose tissue: the role of IL-6 cell membrane receptor.

Only few studies have been addressed to the presence and regulation of C-reactive protein (CRP) gene expression in different districts of adipose tissue, and no study has investigated the role of adipose tissue in presence of inflammation. Therefore, the aim of this study was to investigate the inflammatory involvement of either adipose tissue or adipose cells (adipocytes and stromal cells, respectively) in patients with chronic inflammatory disease, focusing on regional adipose tissue CRP gene expression. Eighteen patients with inflammatory disease and 14 healthy controls were enrolled. All subjects underwent specific surgical procedures. Inflamed and noninflamed patients provided samples of subcutaneous and/or omental adipose tissue. All samples were analyzed by RT-PCR and real-time PCR for specific gene expression. In addition, both adipocytes and stromal cells were studied by real-time PCR and immunoprecipitation to evaluate either gene or protein expression of CRP. Our results (real-time PCR) demonstrated a higher gene expression of CRP, IL-6, and both IL-6 membrane receptors in subcutaneous samples of inflamed patients than in healthy controls. Furthermore, in omental fragments of inflamed patients, an enhanced mRNA abundance of the same genes, compared with subcutaneous, was observed. The results obtained at cellular level did not provide evidence of any difference between adipocytes and stromal cell CRP gene expression, whereas immunoprecipitation demonstrated the presence of CRP in inflamed subjects. These results provide first-time evidence of the involvement of adipose tissue in the course of chronic inflammatory diseases, with a different degree of participation of the different adipose tissue districts.

In vivo modulation of soluble "antagonistic" IL-6 receptor synthesis and release in ESRD.

Soluble gp130 (sgp130) is a soluble circulating receptor of IL-6 with "antagonistic" biologic activity. It is generated independently by either shedding of the extracellular domain of membrane gp130 or alternative mRNA splicing. This study was addressed to clarify the mechanisms underlying sgp130 synthesis and release in patients who undergo regular dialysis treatment (RDT) using dialytic membranes with different biocompatibility. Two groups of RDT patients were enrolled: 11 patients who were treated with cellulosic membranes (C) and 10 patients who were treated with synthetic membranes (S). Ten healthy subjects constituted the control group. Serum samples and peripheral blood mononuclear cells (PBMC) were harvested in all groups (before dialysis in RDT patients). PBMC were cultured for 24 h in the absence or presence of LPS. The serum levels of sgp130 were significantly higher in C group than in control and S patients (C, 603.1 +/- 89.9; control, 396 +/- 49.5; S, 423.4 +/- 27.7 ng/ml; P < 0.01). PBMC from C patients, in the absence of any mitogenic stimulation, released a significantly greater amount of sgp130 as compared with S and control groups (C, 532.6 +/- 161.2; S, 332.4 +/- 148.6; control, 341.4 +/- 125.4 pg/ml; P < 0.01). The sgp130 release was positively correlated with the release of both IL-6 (r = 0.336, P < 0.05) and sIL-6R receptor (r = 0.324, P < 0.05). A significantly higher gp130 gene expression was also observed in unstimulated PBMC from C patients when compared with control and S groups. It is interesting that the expression of the 85-bp exon characteristic of the alternative splicing mRNA for sgp130 was low in all groups. Finally, confocal microscopy analysis showed an increased expression of gp130 on cell surface in unstimulated PBMC from C patients as compared with control and S groups. Our results demonstrate that in patients on RDT with C membranes, the synthesis and release of sgp130 "antagonistic" receptor is significantly increased. This release is seemingly due to a shedding of membrane-bound gp130 receptor. The increased sgp130 release may partially counteract the inflammatory effects caused by IL-6.

Body composition and cardiovascular risk factors in pretransplant hemodialysis patients.

BACKGROUND: Obesity, hyperlipemia and cardiovascular complications contribute to a significant proportion of morbidity and mortality of renal transplant patients and have negative effects on renal survival. Aim of the present study was to evaluate the main abnormalities in body composition and the prevalence of some cardiovascular risk factors in a population of hemodialyzed (HD) patients awaiting renal transplantation. METHODS: We studied 151 HD patients, all included in a waiting list for renal transplantation, 97 males and 54 females, with mean age 47.4+/-12 years. Patients were divided into three groups according to their body mass index (BMI) (kg/m2): 18.5 to 24.9 (normoweight, NW); 25.0 to 29.9 (overweight, OW); > or =30 (obese, OB). The body composition measurements were obtained the day after the mid-week HD session using bioelectrical impedance analysis (BIA). RESULTS: We found that 47 patients were NW (31%), while 56 were OW (37%), and 48 were OB (32%). BIA-measured body cell mass was (BCM) significantly increased in the OW as compared with the NW group (P<0.001), but, of note, no significant difference was found in OB group in comparison with the OW. Total cholesterol and triglycerides plasma levels were significantly elevated in OW and OB patients with respect to NW (P<0.05) and an increased prevalence of diabetes was seen in OB patients (NW: 6%, OW: 5%, OB: 12%). CONCLUSIONS: These data show that a large proportion of patients awaiting renal transplant are overweight or obese and a consistent part of them have other cardiovascular risk factors associated. Furthermore, obese HD patients have a BCM lower than predicted on the basis of BMI and show an altered metabolic profile. A better understanding of the characteristics of patients included in the renal transplant waiting list is crucial in order to design prospective studies that aim to define the proper risk profile for the selection of patients.