Suppressive role of hepatic dendritic cells in concanavalin A-induced hepatitis.

Concanavalin A (Con A)-induced hepatitis is a mouse model of acute autoimmune hepatitis. The aim of this study was to investigate the role of hepatic dendritic cells (DC) in the immune modulation of tissue damage. Almost all hepatic DC were plasmacytoid DC (CD11c+ I-A(low) B220+); however, conventional DC were CD11c+ I-A(high) B220(-). At an early stage (3-6 h) after Con A administration, the number of DC in both the liver and spleen decreased, increasing thereafter (12-24 h) in parallel with hepatic failure. The hepatic CD11c+ DC population contained many CD11b(-) cells, while the majority of splenic CD11c+ DC were CD11b+. After Con A administration, the proportion of I-A+ and CD11b+ cells within the CD11c+ DC population tended to increase in the liver, but not in the spleen. Similarly, expression of the activation markers CD80, CD86 and CD40 by CD11c+ DC increased in the liver, but not in the spleen. Next, adoptive transfer of DC isolated from the liver and spleen was performed 3 h after Con A administration to examine the immunomodulatory function of DC. Only hepatic DC had the ability to suppress hepatic failure. Analysis of cytokine production and subsequent identification of the effector cells showed that hepatic DC achieved this by suppressing the production of interleukin (IL)-12 and IL-2, rather than modulating effector cell function.

Fibroblast growth factor 23 in chronic kidney disease: bridging the gap between bone mineral metabolism and left ventricular hypertrophy.

BACKGROUND: Left ventricular hypertrophy (LVH) is a major cardiovascular complication in chronic kidney disease (CKD) patients. For a successful management of LVH, the comprehensive understanding of the classical and the new emerging factors associated with LVH is of paramount importance. The aim of the present study was to evaluate the clinical correlates of bone mineral metabolism with the occurrence of LVH in nondialyzed CKD patients. METHODS: This cross-sectional study included 96 patients with stages 2-4 CKD. Demographic characteristics, clinical profiles, laboratory tests and transthoracic echocardiogram were performed. RESULTS: LVH was observed in 36% of the patients. Patients with LVH were older, had a higher prevalence of hypertension, and higher levels of intact parathormone, fibroblast growth factor 23 and C-reactive protein. Serum phosphorus, alkaline phosphatase and vitamin D were not associated with the presence of LVH. In the multiple logistic regression analyses only FGF23 remained as a variable independently associated with LVH. CONCLUSION: We confirmed the high prevalence of LVH in nondialyzed CKD patients and showed that FGF23, an early marker of phosphorus load, was an important factor associated with LVH in these patients. Monitoring of FGF23 could be important for the management of LVH in this population.