Paricalcitol Reduces Basal and Lipopolysaccharide-induced (LPS) TNF-alpha and IL-8 Production by Human Peripheral Blood Mononuclear Cells

Overview

Journal Int Urol Nephrol

Publisher Springer

Specialty Nephrology

Date 2009 Mar 5

PMID 19259778

Citations 18

Authors

Theodoros Eleftheriadis

Georgia Antoniadi

Vassilios Liakopoulos

Charalambos Kartsios

Ioannis Stefanidis

Grammati Galaktidou

Affiliations

Soon will be listed here.

Abstract

Introduction: Vitamin D and its analogues proved to exert immunomodulatory effects. Paricalcitol is a vitamin D analogue that is safe. It has been used for years in the treatment of secondary hyperparathyroidism in hemodialysis patients and, importantly, it is less calcemic than vitamin D. In this study the immunomodulatory/anti-inflammatory properties of paricalcitol were evaluated in vitro.

Subject And Methods: Ten healthy volunteers enrolled into the study. Peripheral blood mononuclear cells (PBMC) at a concentration of 10(6) cells per well were cultured for 48 h in the presence or not of lipopolysaccharide (LPS) (100 ng/ml) and in the presence or not of paricalcitol (10(-8) M). TNF-alpha and IL-8 were measured in the supernatants by ELISA.

Results: Basal TNF-alpha concentration (50.3 +/- 22 pg/ml) was reduced by paricalcitol (44.1 +/- 23.2 pg/ml). LPS increased TNF-alpha concentration (150.0 +/- 81.7 pg/ml), but paricalcitol reduced it (121.1 +/- 69.0 pg/ml). The effect of paricalcitol on IL-8 production was more profound. Basal IL-8 concentration (1926 +/- 455 pg/ml) was reduced by paricalcitol (1273 +/- 472 pg/ml). LPS increased IL-8 concentration (2361 +/- 385 pg/ml), but paricalcitol returned it to its basal level (1849 +/- 417 pg/ml).

Conclusion: The in vitro inhibition of transforming growth factor alpha and interleukin 8 by paricalcitol confirms the immunomodulatory properties of this vitamin D analogue.

Citing Articles

Association between Vitamin D Status and Mortality among Adults with Diabetic Kidney Disease.

Xu F, Lu H, Lai T, Lin L, Chen Y J Diabetes Res. 2022; 2022:9632355.

PMID: 35586117 PMC: 9110229. DOI: 10.1155/2022/9632355.

Vitamin D as a Potential Preventive Agent For Young Women's Breast Cancer.

Bernhardt S, Borges V, Schedin P Cancer Prev Res (Phila). 2021; 14(9):825-838.

PMID: 34244152 PMC: 8937000. DOI: 10.1158/1940-6207.CAPR-21-0114.

Exploring the potential effect of paricalcitol on markers of inflammation in de novo renal transplant recipients.

Pihlstrom H, Ueland T, Michelsen A, Aukrust P, Gatti F, Hammarstrom C PLoS One. 2020; 15(12):e0243759.

PMID: 33326471 PMC: 7743930. DOI: 10.1371/journal.pone.0243759.

Anti-Inflammatory Effects of Vitamin D on Human Immune Cells in the Context of Bacterial Infection.

Hoe E, Nathanielsz J, Toh Z, Spry L, Marimla R, Balloch A Nutrients. 2016; 8(12).

PMID: 27973447 PMC: 5188461. DOI: 10.3390/nu8120806.

Calcium-Vitamin D Co-supplementation Affects Metabolic Profiles, but not Pregnancy Outcomes, in Healthy Pregnant Women.

Asemi Z, Samimi M, Amiri Siavashani M, Mazloomi M, Tabassi Z, Karamali M Int J Prev Med. 2016; 7:49.

PMID: 27076887 PMC: 4809130. DOI: 10.4103/2008-7802.177895.

References

Redaelli C, Wagner M, Tien Y, Mazzucchelli L, Stahel P, Schilling M . 1 alpha,25-Dihydroxycholecalciferol reduces rejection and improves survival in rat liver allografts. Hepatology. 2001; 34(5):926-34. DOI: 10.1053/jhep.2001.28705. View

Kamen D, Cooper G, Bouali H, Shaftman S, Hollis B, Gilkeson G . Vitamin D deficiency in systemic lupus erythematosus. Autoimmun Rev. 2006; 5(2):114-7. DOI: 10.1016/j.autrev.2005.05.009. View

Spasovski G . Bone health and vascular calcification relationships in chronic kidney disease. Int Urol Nephrol. 2007; 39(4):1209-16. DOI: 10.1007/s11255-007-9276-9. View

Hullett D, Cantorna M, Redaelli C, Hayes C, Sollinger H, DeLuca H . Prolongation of allograft survival by 1,25-dihydroxyvitamin D3. Transplantation. 1998; 66(7):824-8. DOI: 10.1097/00007890-199810150-00002. View

Mathieu C, Waer M, Laureys J, Rutgeerts O, Bouillon R . Prevention of autoimmune diabetes in NOD mice by 1,25 dihydroxyvitamin D3. Diabetologia. 1994; 37(6):552-8. DOI: 10.1007/BF00403372. View

Larsen C, Kristensen M, Paludan K, Deleuran B, Thomsen M, Zachariae C . 1,25(OH)2-D3 is a potent regulator of interleukin-1 induced interleukin-8 expression and production. Biochem Biophys Res Commun. 1991; 176(3):1020-6. DOI: 10.1016/0006-291x(91)90384-j. View

Lemire J, Ince A, Takashima M . 1,25-Dihydroxyvitamin D3 attenuates the expression of experimental murine lupus of MRL/l mice. Autoimmunity. 1992; 12(2):143-8. DOI: 10.3109/08916939209150321. View

Aguado P, Del Campo M, Garces M, Gonzalez-Casaus M, Bernad M, Gijon-Banos J . Low vitamin D levels in outpatient postmenopausal women from a rheumatology clinic in Madrid, Spain: their relationship with bone mineral density. Osteoporos Int. 2001; 11(9):739-44. DOI: 10.1007/s001980070052. View

Cantorna M, Hullett D, Redaelli C, Brandt C, Sollinger H, DeLuca H . 1,25-Dihydroxyvitamin D3 prolongs graft survival without compromising host resistance to infection or bone mineral density. Transplantation. 1998; 66(7):828-31. DOI: 10.1097/00007890-199810150-00003. View

10.

Hypponen E, Laara E, Reunanen A, Jarvelin M, Virtanen S . Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet. 2001; 358(9292):1500-3. DOI: 10.1016/S0140-6736(01)06580-1. View

11.

Gannage-Yared M, Azoury M, Mansour I, Baddoura R, Halaby G, Naaman R . Effects of a short-term calcium and vitamin D treatment on serum cytokines, bone markers, insulin and lipid concentrations in healthy post-menopausal women. J Endocrinol Invest. 2003; 26(8):748-53. DOI: 10.1007/BF03347358. View

12.

Takahashi K, Horiuchi H, Ohta T, Komoriya K, Ohmori H, Kamimura T . 1 alpha,25-dihydroxyvitamin D3 suppresses interleukin-1beta-induced interleukin-8 production in human whole blood: an involvement of erythrocytes in the inhibition. Immunopharmacol Immunotoxicol. 2002; 24(1):1-15. DOI: 10.1081/iph-120003399. View

13.

Muller K, Haahr P, Diamant M, Rieneck K, Kharazmi A, Bendtzen K . 1,25-Dihydroxyvitamin D3 inhibits cytokine production by human blood monocytes at the post-transcriptional level. Cytokine. 1992; 4(6):506-12. DOI: 10.1016/1043-4666(92)90012-g. View

14.

Cantorna M, Munsick C, Bemiss C, Mahon B . 1,25-Dihydroxycholecalciferol prevents and ameliorates symptoms of experimental murine inflammatory bowel disease. J Nutr. 2000; 130(11):2648-52. DOI: 10.1093/jn/130.11.2648. View

15.

Gelev S, Spasovski G, Dzikova S, Trajkovski Z, Damjanovski G, Amitov V . Vascular calcification and atherosclerosis in hemodialysis patients: what can we learn from the routine clinical practice?. Int Urol Nephrol. 2008; 40(3):763-70. DOI: 10.1007/s11255-008-9379-y. View

16.

Lindberg J, Martin K, Gonzalez E, Acchiardo S, Valdin J, Soltanek C . A long-term, multicenter study of the efficacy and safety of paricalcitol in end-stage renal disease. Clin Nephrol. 2001; 56(4):315-23. View

17.

Redaelli C, Wagner M, Stahel P, Mazzucchelli L, Schmid R, Schilling M . 1alpha,25-dihydroxyvitamin D3 shows strong and additive immunomodulatory effects with cyclosporine A in rat renal allotransplants. Kidney Int. 2002; 61(1):288-96. DOI: 10.1046/j.1523-1755.2002.00101.x. View

18.

Xu H, Soruri A, Gieseler R, Peters J . 1,25-Dihydroxyvitamin D3 exerts opposing effects to IL-4 on MHC class-II antigen expression, accessory activity, and phagocytosis of human monocytes. Scand J Immunol. 1993; 38(6):535-40. DOI: 10.1111/j.1365-3083.1993.tb03237.x. View

19.

Lemire J, Archer D . 1,25-dihydroxyvitamin D3 prevents the in vivo induction of murine experimental autoimmune encephalomyelitis. J Clin Invest. 1991; 87(3):1103-7. PMC: 329907. DOI: 10.1172/JCI115072. View

20.

Gregori S, Casorati M, Amuchastegui S, Smiroldo S, Davalli A, Adorini L . Regulatory T cells induced by 1 alpha,25-dihydroxyvitamin D3 and mycophenolate mofetil treatment mediate transplantation tolerance. J Immunol. 2001; 167(4):1945-53. DOI: 10.4049/jimmunol.167.4.1945. View