No abstract

Ann Rheum Dis 2003;62:952-956 Background: Leptin has been shown to participate in bone remodelling and leptin substitution reported to have a protective effect in experimental septic arthritis. Objective: To assess leptin levels in inflamed joints and plasma of patients with RA. Material and methods: Leptin concentrations were assessed in matched blood and synovial fluid samples from 76 patients with RA. Blood samples from 34 healthy subjects acted as additional controls. Results were analysed and correlated with duration and activity of RA, x ray changes, and treatment at time of sampling. Results: In patients with RA, leptin levels were significantly higher in plasma than in synovial fluid samples obtained simultaneously and higher than in control samples. Plasma and synovial fluid leptin levels correlated strongly. Locally in the joint, leptin levels were related to WBC count. Such a relation was not seen in the bloodstream. Leptin levels were not related to sex, age, or disease duration. Difference between leptin levels in plasma and synovial fluid was greater in non-erosive arthritis (5.1 (SEM 1.2) v 3.7 (0.9) ng/ml, p=0.006), than in patients with erosive joint disease (6.2 (1.0) v 5.4 (0.8) ng/ml, NS). Methotrexate treatment was associated with relatively high plasma leptin levels, while treatment with other DMARDs was associated with lower leptin levels than in patients receiving no DMARD treatment (p=0.0005). Conclusions: Leptin production was significantly increased in patients with RA compared with healthy controls. Synovial fluid leptin levels were significantly lower than in matched plasma samples, suggesting an in situ consumption of this molecule.

Interleukin-1 (IL-1) is a major mediator of inflammation that exerts its biological activities through the IL-1 type I receptor (IL-1RI). The body weights of IL-1RI؊/؊ mice of both sexes started to deviate from those of wild-type mice at 5-6 months of age and were 20% higher at 9 months of age. Visceral and subcutaneous fat mass, measured by dual-energy X-ray absorptiometry and magnetic resonance imaging, was markedly (1.5-to 2.5-fold) increased. Lean body mass and crown-rump length were also slightly (11 and 5%, respectively) increased, as was serum IGF-I. Obese IL-1RI؊/؊ mice were insulin resistant, as evidenced by hyperinsulinemia, decreased glucose tolerance, and insulin sensitivity. To elucidate the mechanisms for the development of obesity, young preobese IL-1RI ؊/؊ mice were investigated. They showed decreased suppression of body weight and food intake in response to systemic leptin treatment. The decreased leptin responsiveness was even more pronounced in older obese animals. Moreover, spontaneous locomotor activity and fat utilization, as measured by respiratory quotient, were decreased in preobese IL-1RI ؊/؊ mice. In conclusion, lack of IL-1RI-mediated biological activity causes mature-onset obesity. This obese phenotype is preceded by decreased leptin sensitivity, fat utilization, and locomotor activity. Diabetes 55: [1205][1206][1207][1208][1209][1210][1211][1212][1213] 2006 T he prevalence of obesity is growing rapidly in many parts of the world and reaching epidemic proportions in several developed countries (1). Overweight and obesity are associated with increased risk of metabolic disorders, such as type 2 diabetes and hyperlipidemia, and thereby increased risk of cardiovascular mortality. Although the regulation of body weight and body composition involves input from lifestyle and environment, compelling scientific evidence indicates that propensity to develop obesity is in large part attributable to genetic factors. Over the last decade, the study of different transgenic and knockout mouse models has contributed to the identification of new factors involved in the complex mechanisms regulating energy balance and to the clarification of the contribution of genetics to obesity (2,3). Moreover, a number of human genes have been identified in which major missense or nonsense mutations as well as genetic variations are associated with obesityrelated phenotypes. Many of these genetic variants have occurred in molecules identical or similar to those identified as a cause of obesity in rodents, supporting their involvement in the regulation of body weight homeostasis also in humans (4).Interleukin-1 (IL-1) is a major mediator of inflammation and exerts effects on the neuro-immuno-endocrine system (5). Infection, injury, and inflammation are associated with negative energy balance, characterized by reduced food intake, weight loss, increased thermogenesis, and fever. IL-1 could be of importance for these effects, as peripheral or central injection of IL-1 induces a marked rise in body temperature (f...

Table of contentsP001 - Sepsis impairs the capillary response within hypoxic capillaries and decreases erythrocyte oxygen-dependent ATP effluxR. M. Bateman, M. D. Sharpe, J. E. Jagger, C. G. EllisP002 - Lower serum immunoglobulin G2 level does not predispose to severe flu.J. Solé-Violán, M. López-Rodríguez, E. Herrera-Ramos, J. Ruíz-Hernández, L. Borderías, J. Horcajada, N. González-Quevedo, O. Rajas, M. Briones, F. Rodríguez de Castro, C. Rodríguez GallegoP003 - Brain protective effects of intravenous immunoglobulin through inhibition of complement activation and apoptosis in a rat model of sepsisF. Esen, G. Orhun, P. Ergin Ozcan, E. Senturk, C. Ugur Yilmaz, N. Orhan, N. Arican, M. Kaya, M. Kucukerden, M. Giris, U. Akcan, S. Bilgic Gazioglu, E. TuzunP004 - Adenosine a1 receptor dysfunction is associated with leukopenia: A possible mechanism for sepsis-induced leukopeniaR. Riff, O. Naamani, A. DouvdevaniP005 - Analysis of neutrophil by hyper spectral imaging - A preliminary reportR. Takegawa, H. Yoshida, T. Hirose, N. Yamamoto, H. Hagiya, M. Ojima, Y. Akeda, O. Tasaki, K. Tomono, T. ShimazuP006 - Chemiluminescent intensity assessed by eaa predicts the incidence of postoperative infectious complications following gastrointestinal surgeryS. Ono, T. Kubo, S. Suda, T. Ueno, T. IkedaP007 - Serial change of c1 inhibitor in patients with sepsis – A prospective observational studyT. Hirose, H. Ogura, H. Takahashi, M. Ojima, J. Kang, Y. Nakamura, T. Kojima, T. ShimazuP008 - Comparison of bacteremia and sepsis on sepsis related biomarkersT. Ikeda, S. Suda, Y. Izutani, T. Ueno, S. OnoP009 - The changes of procalcitonin levels in critical patients with abdominal septic shock during blood purificationT. Taniguchi, M. OP010 - Validation of a new sensitive point of care device for rapid measurement of procalcitoninC. Dinter, J. Lotz, B. Eilers, C. Wissmann, R. LottP011 - Infection biomarkers in primary care patients with acute respiratory tract infections – Comparison of procalcitonin and C-reactive proteinM. M. Meili, P. S. SchuetzP012 - Do we need a lower procalcitonin cut off?H. Hawa, M. Sharshir, M. Aburageila, N. SalahuddinP013 - The predictive role of C-reactive protein and procalcitonin biomarkers in central nervous system infections with extensively drug resistant bacteriaV. Chantziara, S. Georgiou, A. Tsimogianni, P. Alexandropoulos, A. Vassi, F. Lagiou, M. Valta, G. Micha, E. Chinou, G. MichaloudisP014 - Changes in endotoxin activity assay and procalcitonin levels after direct hemoperfusion with polymyxin-b immobilized fiberA. Kodaira, T. Ikeda, S. Ono, T. Ueno, S. Suda, Y. Izutani, H. ImaizumiP015 - Diagnostic usefullness of combination biomarkers on ICU admissionM. V. De la Torre-Prados, A. Garcia-De la Torre, A. Enguix-Armada, A. Puerto-Morlan, V. Perez-Valero, A. Garcia-AlcantaraP016 - Platelet function analysis utilising the PFA-100 does not predict infection, bacteraemia, sepsis or outcome in critically ill patientsN. Bolton, J. Dudziak, S. Bonney, A. Tridente, P. NeeP017 - Extracellular histone H3 levels are in...

No abstract