Digestive Diseases and Sciences

, Volume 57, Issue 1, pp 182–188

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

  • Chong Zhang
  • Lianrong Zhao
  • Li Ma
  • Cheng Lv
  • Yang Ding
  • Tingting Xia
  • Jingyan Wang
  • Xiaoguang Dou
Original Article



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.


Vitamin D Vitamin D receptor LL-37 Cirrhosis Spontaneous bacterial peritonitis 


  1. 1.
    Ghassemi S, Garcia-Tsao G. Prevention and treatment of infections in patients with cirrhosis. Best Pract Res Clin Gastroenterol. 2007;21:77–93.PubMedCrossRefGoogle Scholar
  2. 2.
    Homann C, Varming K, Hogasen K, et al. Acquired C3 deficiency in patients with alcoholic cirrhosis predisposes to infection and increased mortality. Gut. 1997;40:544–549.PubMedGoogle Scholar
  3. 3.
    Ono Y, Watanabe T, Matsumoto K, Ito T, Kunii O, Goldstein E. Opsonophagocytic dysfunction in patients with liver cirrhosis and low responses to tumor necrosis factor-α and lipopolysaccharide in patients’ blood. J Infect Chemother. 2004;10:200–207.PubMedGoogle Scholar
  4. 4.
    Fiuza C, Salcedo M, Clemente G, Tellado JM. In vivo neutrophil dysfunction in cirrhotic patients with advanced liver disease. J Infect Dis. 2000;182:526–533.PubMedCrossRefGoogle Scholar
  5. 5.
    Pappa HM, Bern E, Kamin D, Grand RJ. Vitamin D status in gastrointestinal and liver disease. Curr Opin Gastroenterol. 2008;24:176–183.PubMedCrossRefGoogle Scholar
  6. 6.
    Arteh J, Narra S, Nair S. Prevalence of vitamin D deficiency in chronic liver disease. Dig Dis Sci. 2010;55:2624–2628.PubMedCrossRefGoogle Scholar
  7. 7.
    Liu PT, Stenger S, Li H, et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science. 2006;311:1770–1773.PubMedCrossRefGoogle Scholar
  8. 8.
    Zanetti M. Cathelicidins, multifunctional peptides of the innate immunity. J Leukoc Biol. 2004;75:39–48.PubMedCrossRefGoogle Scholar
  9. 9.
    Iimura M, Gallo RL, Hase K, Miyamoto Y, Eckmann L, Kagnoff MF. Cathelicidin mediates innate intestinal defense against colonization with epithelial adherent bacterial pathogens. J Immunol. 2005;174:4901–4907.PubMedGoogle Scholar
  10. 10.
    D’Aldebert E, Biyeyeme Bi Mve MJ, Mergey M, et al. Bile salts control the antimicrobial peptide cathelicidin through nuclear receptors in the human biliary epithelium. Gastroenterology. 2009;136:1435–1443.PubMedCrossRefGoogle Scholar
  11. 11.
    Gombart AF, Bhan I, Borregaard N, et al. Low plasma level of cathelicidin antimicrobial peptide (hCAP18) predicts increased infectious disease mortality in patients undergoing hemodialysis. Clin Infect Dis. 2009;48:418–424.PubMedCrossRefGoogle Scholar
  12. 12.
    Møller S, Laigaard F, Olgaard K, Hemmingsen C. Effect of 1, 25-dihydroxy-vitamin D3 in experimental sepsis. Int J Med Sci. 2007;4:190–195.PubMedGoogle Scholar
  13. 13.
    Fisher L, Fisher A. Vitamin D and parathyroid hormone in outpatients with noncholestatic chronic liver disease. Clin Gastroenterol Hepatol. 2007;5:513–520.PubMedCrossRefGoogle Scholar
  14. 14.
    Miller J, Gallo RL. Vitamin D and innate immunity. Dermatol Ther. 2010;23:13–22.PubMedCrossRefGoogle Scholar
  15. 15.
    Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266–281.PubMedCrossRefGoogle Scholar
  16. 16.
    Wang TT, Nestel FP, Bourdeau V, et al. Cutting edge: 1, 25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J Immunol. 2004;173:2909–2912.PubMedGoogle Scholar
  17. 17.
    Leandro AC, Rocha MA, Cardoso CS, Bonecini-Almeida MG. Genetic polymorphisms in vitamin D receptor, vitamin D-binding protein, Toll-like receptor 2, nitric oxide synthase 2, and interferon-gamma genes and its association with susceptibility to tuberculosis. Braz J Med Biol Res. 2009;42:312–322.PubMedCrossRefGoogle Scholar
  18. 18.
    Yamshchikov AV, Kurbatova EV, Kumari M, et al. Vitiman D status and antimicrobial peptide cathelicidin (LL-37) concentrations in patients with active pulmonary tuberculosis. Am J Clin Nutr. 2010;92:603–611.PubMedCrossRefGoogle Scholar
  19. 19.
    Selvaraj P, Prabhu Anand S, Harishankar M, Alagarasu K. Plasma 1, 25 dihydroxy vitamin D3 level and expression of vitamin D receptor and cathelicidin in pulmonary tuberculosis. J Clin Immunol. 2009;29:470–478.PubMedCrossRefGoogle Scholar
  20. 20.
    Cannell JJ, Vieth R, Umhau JC, et al. Epidemic influenza and vitamin D. Epidemiol Infect. 2006;134:1129–1140.PubMedCrossRefGoogle Scholar
  21. 21.
    Alagarasu K, Selvaraj P, Swaminathan S, Narendran G, Narayanan PR. 5′ regulatory and 3′ untranslated region polymorphisms of vitamin D receptor gene in south Indian HIV and HIV-TB patients. J Clin Immunol. 2009;29:196–204.PubMedCrossRefGoogle Scholar
  22. 22.
    Jeng L, Yamshchikov AV, Judd SE, et al. Alterations in vitamin D status and anti-microbial peptide levels in patients in the intensive care unit with sepsis. J Transl Med. 2009;7:28.PubMedCrossRefGoogle Scholar
  23. 23.
    Bouillon R, Carmeliet G, Verlinden L, et al. Vitamin D and human health: lessons from vitamin D receptor null mice. Endocr Rev. 2008;29:726–776.PubMedCrossRefGoogle Scholar
  24. 24.
    Pramanik R, Asplin JR, Lindeman C, Favus MJ, Bai S, Coe FL. Lipopolysaccharide negatively modulates vitamin D action by down-regulating expression of vitamin D-induced VDR in human monocytic THP-1 cells. Cell Immunol. 2004;232:137–143.PubMedCrossRefGoogle Scholar
  25. 25.
    Muñoz L, Albillos A, Nieto M, et al. Mesenteric Th1 polarization and monocyte TNF-alpha production: first steps to systemic inflammation in rats with cirrhosis. Hepatology. 2005;42:411–419.PubMedCrossRefGoogle Scholar
  26. 26.
    Francés R, Zapater P, González-Navajas JM, et al. Bacterial DNA in patients with cirrhosis and noninfected ascites mimics the soluble immune response established in patients with spontaneous bacterial peritonitis. Hepatology. 2008;47:978–985.PubMedCrossRefGoogle Scholar
  27. 27.
    Ong PY, Ohtake T, Brandt C, et al. Endogenous antimicrobial peptides and skin infections in atopic dermatitis. N Engl J Med. 2002;347:1151–1160.PubMedCrossRefGoogle Scholar
  28. 28.
    Nomura I, Goleva E, Howell MD, et al. Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes. J Immunol. 2003;171:3262–3269.PubMedGoogle Scholar
  29. 29.
    Howell MD, Novak N, Bieber T, et al. Interleukin-10 downregulates anti-microbial peptide expression in atopic dermatitis. J Invest Dermatol. 2005;125:738–745.PubMedCrossRefGoogle Scholar
  30. 30.
    Veldman CM, Cantorna MT, DeLuca HF. Expression of 1, 25-dihydroxyvitamin D(3) receptor in the immune system. Arch Biochem Biophys. 2000;374:334–338.PubMedCrossRefGoogle Scholar
  31. 31.
    Adams JS, Ren S, Liu PT, et al. Vitamin D-directed rheostatic regulation of monocyte antibacterial responses. J Immunol. 2009;182:4289–4295.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Chong Zhang
    • 1
  • Lianrong Zhao
    • 1
  • Li Ma
    • 1
  • Cheng Lv
    • 1
  • Yang Ding
    • 1
  • Tingting Xia
    • 1
  • Jingyan Wang
    • 1
  • Xiaoguang Dou
    • 1
  1. 1.Department of Infectious DiseasesShengjing Hospital Affiliated to China Medical UniversityShenyangChina

Personalised recommendations