Vitamin D Status and Expression of Vitamin D Receptor and LL-37 in Patients with Spontaneous Bacterial Peritonitis

Abstract

Vitamin D, which exerts its effect through vitamin D receptor (VDR), and LL-37, a vitamin D-dependent antimicrobial peptide, are involved in many infectious diseases. The objective of this study was to evaluate whether vitamin D status and expressions of VDR and LL-37 are involved in the pathogenesis of spontaneous bacterial peritonitis (SBP). Serum and ascitic fluid 25-dihydroxyvitamin D [25(OH)D] concentrations and levels of VDR and LL-37 in peritoneal leukocytes were measured by ELISA and real-time PCR methods in cirrhotic patients with SBP (n = 19) and cirrhotic patients with simple ascites (n = 28). The correlations between these levels and clinical variables were evaluated. Cirrhotic patients with ascites showed low vitamin D concentrations in both serum and ascitic fluid. Lower serum vitamin D concentrations were observed in cirrhotic patients with Child-Pugh C class. 25(OH)D concentrations in ascitic fluid were positive correlated with that in serum (r = 0.74, P < 0.001). The SBP group showed significantly higher levels of both VDR and LL-37 mRNA expressions in peritoneal leukocytes than the simple ascites group (P = 0.005 and P = 0.003, respectively). In the SBP group, VDR and LL-37 expressions in peritoneal leukocytes were positively correlated (r = 0.70, P = 0.001). Vitamin D insufficiency was universal among cirrhotic patients with ascites, and the situation was more severe with more serious cirrhosis. Expressions of peritoneal leukocytes VDR and LL-37 genes were simultaneously up-regulated in cirrhotic patients with SBP when compared with cirrhotic patients with simple ascites. It is indicated that the vitamin D-VDR system and its downstream gene, LL-37, are involved in the pathogenesis and antibacterial immune response to SBP.