Difference of Vitamin D and Interleukin-6 Levels in Children with Steroid- Resistant, Steroid-Sensitive and Idiopathic Nephrotic Syndrome
DOI:
https://doi.org/10.11594/jtls.09.02.07Keywords:
interleukin-6, nephrotic syndrome, vitamin D levelAbstract
Idiopathic nephrotic syndrome (INS) is the most prevalent autoimmune glomerular disease in children and its pathogenesis is correlated with high level of interleukin 6 (IL-6) and low level of vitamin D. This study was aimed to investigate the difference of vitamin D and IL-6 level in steroid resistant nephrotic syndrome (SRNS), steroid sensitive (SSNS), and idiopathic nephrotic syndrome (INS). This research was designed as cross sectional involving 45 subjects which then divided into 3 groups as follows: SRNS, SSNS, and INS. A level of serum 25 (OH)D was measured by Enzyme-linked Immuno Assay Method then categorized as sufficiency, insufficiency, and deficiency. Level of IL-6 serum was measured by ELISA method. Results showed that IL-6 level was significantly different among three groups, in which SRNS had the highest value (ANOVA, p < 0.05). Further analysis demonstrated that IL-6 level correlated with steroid resistance (Spearman correlation test, p = 0.000, r = 0.692). Vitamin D status was significantly different among three groups (Chi square, p = 0.03) and associated with steroid resistance (Spearman correlation test, p = 0.000, r = 0.568). Moreover, IL-6 level associated with 25 (OH) D level in SRNS group (Pearson correlation test, p = 0.020, r = 0.591) but not in the SSNS and INS group. We conclude that IL-6 levels were significantly higher in SRNS group as compared to other groups. Otherwise, vitamin D status were significantly lower in SRNS compared with other groups. An IL-6 level was negatively correlated with vitamin D status in patients with NS, specifically in SRNS group.
References
Bagga A (2008) Management of steroid sensitive nephrotic: Revised guidelines. Indian Pediatrics 45 (3): 203 – 214.
Zhang J, Pippin JW, Krofft RD et al. (2013) Podocyte repopulation by renal progenitor cells following glucocorticoids treatment in experimental FSGS. Renal Physiology 304 (11): 1375 – 1389. doi: 10.1152/ajprenal.00020.2013.
UKK Nefrologi Ikatan Dokter Anak Indonesia (2008) Tatalaksana sindrom nefrotik idiopatik pada anak. Badan Penerbit Ikatan Dokter Anak Indonesia, Jakarta
Krisni (2007) Pola penyakit ginjal pada anak di RS Saiful Anwar Malang tahun 2002-2006 [oral presentation]. Pertemuan Ilmiah Tahunan Ilmu Kesehatan Anak Ikatan Dokter Anak Indonesia (PIT IKA-IDAI), Yogyakarta.
Hafez MA, Shimada M, Lee PY et al. (2009) Idiopathic nephrotic syndrome and atopy: Is there a common link? American Journal of Kidney Disease 54 (5): 945 – 953. doi: 10.1053/j.ajkd.2009.03.019.
Kaneko K (2009) Pathogenesis in childhood idiopathic nephrotic syndrome: an update of patchwork. Current Pediatric Review 5 (1): 56 – 64. doi: 10.2174/157339609787587537.
Wang L, Li Q, Wang L et al. (2013) The role of Th17/IL-17 in the pathogenesis of primary nephrotic syndrome in children. Kidney & Blood Pressure Reserach 37 (4-5): 332 – 345. doi: 10.1159/000350161.
Madani H, Bazaraa HM, Rady HI (2014) Association of cytokine genes polymorphisms and the response to corticosteroid therapy in children with idiopathic nephrotic syndrome: A pilot study in Egypt. International Research Journal of Medicine and Medical Sciences 2 (4): 84 – 90.
Chen WP, Lin CY (1994) Augmented expression of interleukin-6 and interleukin-1 genes in the mesangium of IgM mesangial nephropathy. Nephron 68: 10 – 19. doi: 10.1159/000188217.
Yu YW, Ying ZQ (2005) Serum and urinary interleukin-6 levels in children with primary nephrotic syndrome. Chinese Journal of Contemporary Pediatrics 7 (6): 493 – 494.
Perreira Wde F, Brito-Melo GE, Guimaraes FT et al. (2014) The role of the immune system in idiopathic nephrotic syndrome: a review of clinical and experimental studies. Inflammation Research 63 (1): 1-12.
Ginanjar E, Sumariyono SS, Setiyohadi B (2007) Vitamin D and autoimmune disease. Acta Medica Indonesiana - The Indonesian Journal of Internal Medicine 39 (3): 133-141.
Takeda M, Yamashita T, Sasaki N et al. (2010) Oral administration of an active form of vitamin D3 (calcitriol) decreases atherosclerosis in mice by inducing regulatory T cells and immature dendritic cells with tolerogenic func-tions. Arteriosclerosis, Thrombosis, and Vascular Biology 30 (12): 2495 – 2503. doi: 10.1161/atvbaha.110.215459.
Baeke F, Takiishi T, Korf H et al. (2010) Vitamin D: Modulator of the immune system. Current Opinion in Pharmacology 10: 482 – 496. doi: 10.1016/j.coph.2010.04.001.
Hewison M (2010) Vitamin D and the immune system: new perspective on an old theme. Endocrinology and Metabolism Clinics of North America 39: 365 – 379. doi: 10.1016/j.ecl.2010.02.010.
White JH (2008) Vitamin D signaling, infectious diseases, and regulation of innate immunity. Infection and Immunity 76 (9): 3837 – 3843. doi: 10.1128/iai.00353-08.
Terrier B, Buzyn A, Hummel A et al. (2006) Serum monoclonal component and nephrotic syndrome--it is not always amyloidosis. Diagnosis: WM complicated by retroperitoneal and renal infiltration and associated with a minimal change disease. Nephrology Dialysis Transplantation 21 (11): 3327 – 3329. doi: 10.1093/ndt/gfl467.
Urry Z, Chambers EM, Xytrakis E et al. (2012) The role of 1α,25-dihydroxyvitamin D3 and cytokines in the promotion of distinct Foxp3+ and IL-10+CD4+ T cells. European Journal of Immunology 42 (10): 2697 – 2708. doi: 10.1002/eji.201242370.
Xytrakis E, Kusumakar S, Baswell S et al. (2006) Reversing the defective induction of IL-10-secreting regulatory T cells in glucocorticoid-resistant asthma patients. Journal of Clinical Investigation 116: 146 – 155. doi: 10.1172/jci21759.
Cho Y, Hyun SH, Kang GH, Cheong IH (2013) Prevalence of 25(OH) vitamin D insufficiency and deficiency in pediatric patients on chronic dialysis. Peritoneal Dialysis International 33 (4): 398 – 404. doi: 10.3747/pdi.2011.00246.
Salsano ME, Graziano L, Luongo I et al. (2007) Atopy in childhood idiopathic nephrotic syndrome. Acta Paediatrica Oslo Norwegia 96: 561 – 566. doi: 10.1111/j.1651-2227.2007.00154.x.
Ece A, Colpan L, et al. (1999) Serum levels of interleukin IL-1β, sIL-2R, Il-6, IL-8, and TNF-α in children with idiopathic nephrotic syndrome. SDU Tip Fakultesi Dergisi 6 (2): 45 – 48.
Youn YS, Lim HH, Lee JH (2012) The clinical characteristics of steroid responsive nephrotic syndrome of children according to the serum immunoglobulin E levels and cytokines. Yonsei Medical Journal 53: 715 – 722. doi: 10.3349/ymj.2012.53.4.715.
Iwakura Y, Ishigame H (2006) The IL-23/IL-17 axis in inflammation. Journal of Clinical Investigation 116 (5): 1218 – 1222. doi: 10.1172/jci28508.
Shao XS, Yang XQ, Zhao XD et al. (2009) The prevalence of Th17 cells and FOXP3 regulate T cells (Treg) in children with primary nephrotic syndrome. Pediatric Nephrology 24 (9): 1683 – 1690. doi: 10.1007/s00467-009-1194-x.
Pociask DA, Kolls JK (2010) Integral role of integrins in Th17 development. Journal of Clinical Investigation 120 (12): 4185 – 4187. doi: 10.1172/jci45450.
Zhou TB, Lin N, Qin YH, Liu YG (2014) Distribution of pathological finding in the children with nephrotic syndrome from Guangxi. Saudi Journal of Kidney Disease and Transplantation 25: 684 – 688. doi: 10.4103/1319-2442.132240.
Lal G, Jonathan SB (2009) Epigenetic mechanisms of regulation on Foxp3 expression. Blood 114: 3727 – 3735. doi: 10.1182/blood-2009-05-219584.
Fujimoto M, Nakano M, Terabe F et al. (2011) The influence of excessive IL-6 production in vivo on the development and function of Foxp3+ regulatory T cells. Journal of Immunology 186: 32 – 40. doi: 10.4049/jimmunol.0903314.
Handono K, Hasanah DY, Mawarti H (2013) The associations among serum levels of vitamin D, TGF-β/IL-6 balance and Treg/Th17 balance in systemic lupus erythematosus patients in Indonesia. International Journal of Biochemistry and Biotechnology 2 (9): 490 – 496.
Tanaka T, Kishimoto T (2012) Targeting interleukin-6: all the way to treat autoimmune and inflammatory disease. International Journal of Biological Sciences 8 (9): 1227 – 1236. doi: 10.7150/ijbs.4666.
Poh BK, Rojroongwasinkul N, Nguyen BKL et al. (2016) 25-
hydroxy-vitamin D demography and the risk of vitamin D insufficiency in the South East Asian Nutrition Surveys (SEANUTS). Asia Pacific Journal of Clinical Nutrition 25: 538–548. doi: 10.3390/nu10060759.
Septarini AD, Tambunan T, Amalia P (2012) Calcium and vitamin D supplementation in children with frequently relapsing and steroid-dependent nephrotic syndrome. The Indonesian Journal of Pediatrics and Perinatal Medicine 52 (1): 16 – 21. doi: 10.14238/pi53.1.2012.04.
Esmaeeili M, Azarfar A, Hoseinalizadeh S (2015) Calcium and vitamin D metabolism in pediatric nephrotic syndrome; an update on the existing literature. International Journal of Pediatric 3: 103 – 109.
Nielsen CA, Jensen JEB, Cortes D (2015) Vitamin D status is insufficient in the majority of children at diagnosis of nephrotic syndrome. Danish Medical Journal 61: 1 – 5.
Weng FL, Shults J, Herskovitz RM et al. (2005) Vitamin D insufficiency in steroid-sensitive nephrotic syndrome in remission. Pediatric Nephrology 20 (1): 56 – 63. doi: 10.1007/s00467-004-1694-7.
Banerjee S, Basu S, Sengupta J (2013) Vitamin D in nephrotic syndrome remission: A case-control study. Pediatric Nephrology 28: 1983 – 1989.
Jirapongsananuruk O, Melamed I, Leung DY (2000) Additive immunosuppressive effects of 1,25-dihydroxyvitamin D3 and corticosteroids on Th1, but not Th2, responses. Journal of Allergy and Clinical Immunol-ogy 106: 981 – 985. doi: 10.1067/mai.2000.110101.
Nonn L, Peng L, Feldman D, Peehl DM (2006) Cancer prevention by vitamin D protein kinase phosphatase 5: Implication for prostate production in normal prostate cells via mitogen-activated inhibition of p38 by vitamin D reduces Interleukin-6. Cancer Research 66: 4515 – 4524. doi: 10.1158/0008-5472.can-05-3796.
Joshi S, Pantalena LC, Liu XK et al. (2011) 1,25-dihydroxyvitamin D3 ameliorates Th17 autoimmunity via transcriptional modulation of interleukin-17A. Molecular and Cellular Biology 31 (17): 3653 – 3669. doi: 10.1128/mcb.05020-11.
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