Serum levels of IL-6, TNF-α, and YKL-40 in patients with stage I multiple myeloma

Esmaeilzadeh, Zeinab; Kheradmand, Fatemeh; Rasmi, Yousef; Khadem-Ansari, Mohammad Hassan

doi:10.13183/rabms.6.3.160

Volume 6, Issue 3 (July 2020) Journal of Research in Applied and Basic Medical Sciences 2020, 6(3): 160-166 | Back to browse issues page

‎ 10.13183/rabms.6.3.160

Mendeley

Zotero

RefWorks

Esmaeilzadeh Z, Kheradmand F, Rasmi Y, Khadem-Ansari M H. Serum levels of IL-6, TNF-α, and YKL-40 in patients with stage I multiple myeloma. Journal of Research in Applied and Basic Medical Sciences 2020; 6 (3) :160-166
URL: http://ijrabms.umsu.ac.ir/article-1-105-en.html

Serum levels of IL-6, TNF-α, and YKL-40 in patients with stage I multiple myeloma

Zeinab Esmaeilzadeh

, Fatemeh Kheradmand

, Yousef Rasmi

, Mohammad Hassan Khadem-Ansari ^*

Department of Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran , mhansari1@gmail.com

Abstract: (1912 Views)

Background & Aims: Multiple myeloma (MM) is a type of plasma cell malformation accounting for 10% of the blood cancers with unknown ethiopathology. MM causes changes in inflammatory proteins. The aim of this study was to evaluate the serum levels of IL-6, TNF-α, and YKL-40 in patients with stage I MM.
Materials & Methods: This case-control study was performed on 28 patients with stage I MM including 14 males and 14 females with mean age of 62.11 ± 6.71 years and 40 individuals as controls including 20 males and 20 females with mean age of 60.25 ± 4.81 years matched in both age and sex. Serum concentrations of inflammatory factors including IL-6, TNF-α and YKL-40 were measured using the sandwich Enzyme Linked Immunosorbent Assay (ELISA) method and the data were analyzed using SPSS software.
Results: The serum levels of IL-6 in patients with stage I MM (7.42±5.89 pg/ml) were significantly higher compared to the control group (1.67±1.08 pg/ml); (p< 0.0001). Also, the serum levels of YKL-40 in the patients (45.86 ± 9.14 ng/ml) were significantly higher compared to the control group (35.87 ± 11.2 ng/ml); (p <0.0001). Also, the levels of TNF-α (8.02±1.75 pg/ml) were slightly high compared to the control group (7.77 ± 1.91 pg/ml); (p=0.419).
Conclusion: According to the results in MM, inflammatory proteins such as YKL-40 andIL-6 are the major growth factor of the myeloma cells and help their survival.

Keywords: Multiple myeloma, IL-6, TNF-α, YKL-40

Full-Text [PDF 403 kb] (1193 Downloads)

Type of Study: orginal article | Subject: Special

References

1. Kyle RA, Rajkumar SV. Multiple myeloma. Blood. 2008;111(6):2962-72. [DOI:10.1182/blood-2007-10-078022] [PMID] [PMCID]

2. San Miguel JF, Gutiérrez NC, Mateo G, Orfao A. Conventional diagnostics in multiple myeloma. Eur J Cancer. 2006;42(11):1510-9. [DOI:10.1016/j.ejca.2005.11.039] [PMID]

3. Cook R. Introduction: multiple myeloma. JMCP. 2008;14(7 Supp A):4-6. [DOI:10.18553/jmcp.2008.14.S7-A.4] [PMID]

4. Silvestris F, Ciavarella S, De Matteo M, Tucci M, Dammacco F. Bone-resorbing cells in multiple myeloma: osteoclasts, myeloma cell polykaryons, or both? Oncologist. 2009;14(3):264-75. [DOI:10.1634/theoncologist.2008-0087] [PMID]

5. Terpos E, Sezer O, Croucher P, Dimopoulos M-A. Myeloma bone disease and proteasome inhibition therapies. Blood. 2007;110(4):1098-104. [DOI:10.1182/blood-2007-03-067710] [PMID]

6. Kyle RA, Rajkumar SV. Multiple Myeloma. N Engl J Med. 2004;351(18):1860-73. [DOI:10.1056/NEJMra041875] [PMID]

7. Terpos E. Biochemical markers of bone metabolism in multiple myeloma. Cancer Treat Rev. 2006;32 Suppl 1:15-9. [DOI:10.1016/S0305-7372(06)80004-6]

8. Dib IEH, Mélanie G, Valery S, Romuald M, Michel B, Kamel S. Multiple myeloma cells directly stimulate bone resorption in vitro by down-regulating mature osteoclast apoptosis. Leuk Res. 2008;32(8):1279-87. [DOI:10.1016/j.leukres.2007.12.018] [PMID]

9. Linet MS, McLaughlin JK, Hsing AW, Wacholder S, Chien HTC, Schuman LM, et al. Is cigarette smoking a risk factor for non-Hodgkin's lymphoma or multiple myeloma? Results from the Lutheran Brotherhood Cohort Study. Leuk Res. 1992;16(6-7):621-4. [DOI:10.1016/0145-2126(92)90011-U]

10. Tollerud DJ, Brinton LA, Stone B, Tobacman JK, Blattner WA. Mortality from multiple myeloma among North Carolina furniture workers. J Natl Cancer Inst. 1985;74(4):799-801.

11. Greipp PR, Miguel JS, Durie BG, Crowley JJ, Barlogie B, Bladé J, et al. International staging system for multiple myeloma. J Clin Oncol. 2005;23(15):3412-20. [DOI:10.1200/JCO.2005.04.242] [PMID]

12. Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos M-V, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15(12):e538-e48. [DOI:10.1016/S1470-2045(14)70442-5]

13. Abroun S, Ishikawa H, Tsuyama N, Liu S, Li F-J, Otsuyama K-i, et al. Receptor synergy of interleukin-6 (IL-6) and insulin-like growth factor-I in myeloma cells that highly express IL-6 receptor α. Blood. 2004;103(6):2291-8. [DOI:10.1182/blood-2003-07-2187] [PMID]

14. Kawano M, Hirano T, Matsuda T, Taga T, Horii Y, Iwato K, et al. Autocrine generation and requirement of BSF-2/IL-6 for human multiple myelomas. Nature. 1988;332(6159):83-5. [DOI:10.1038/332083a0] [PMID]

15. Thomas X, Anglaret B, Magaud J-P, Epstein J, Archimbaud E. Interdependence between cytokines and cell adhesion molecules to induce interleukin-6 production by stromal cells in myeloma. Leuk Lymphoma. 1998;32(1-2):107-19. [DOI:10.3109/10428199809059251] [PMID]

16. Hideshima T, Chauhan D, Schlossman R, Richardson P, Anderson KC. The role of tumor necrosis factor [alpha] in the pathophysiology of human multiple myeloma: therapeutic applications. Oncogene. 2001;20(33):4519. [DOI:10.1038/sj.onc.1204623] [PMID]

17. Fràter-Schröder M, Risau W, Hallmann R, Gautschi P, Böhlen P. Tumor necrosis factor type alpha, a potent inhibitor of endothelial cell growth in vitro, is angiogenic in vivo. Proceedings of the National Academy of Sciences. 1987;84(15):5277-81. [DOI:10.1073/pnas.84.15.5277] [PMID] [PMCID]

18. Lichtenstein A, Berenson J, Norman D, Chang M-P, Carlile A. Production of cytokines by bone marrow cells obtained from patients with multiple myeloma. Blood. 1989;74(4):1266-73. https://doi.org/10.1182/blood.V74.4.1266.bloodjournal7441266 [DOI:10.1182/blood.V74.4.1266.1266] [PMID]

19. Jurišić V, Čolović M. Correlation of sera TNF-α with percentage of bone marrow plasma cells, LDH, β2-microglobulin, and clinical stage in multiple myeloma. Med Oncol. 2002;19(3):133-9. [DOI:10.1385/MO:19:3:133]

20. Bergmann OJ, Johansen JS, Klausen TW, Mylin AK, Kristensen JS, Kjeldsen E, et al. High serum concentration of YKL-40 is associated with short survival in patients with acute myeloid leukemia. Clin Cancer Res. 2005;11(24):8644-52. [DOI:10.1158/1078-0432.CCR-05-1317] [PMID]

21. Mylin AK, Abildgaard N, Johansen JS, Andersen NF, Heickendorff L, Standal T, et al. High serum YKL‐40 concentration is associated with severe bone disease in newly diagnosed multiple myeloma patients. Eur J Haematol. 2008;80(4):310-7. [DOI:10.1111/j.1600-0609.2007.01027.x] [PMID]

22. Mylin AK, Andersen NF, Johansen JS, Abildgaard N, Heickendorff L, Standal T, et al. Serum YKL‐40 and bone marrow angiogenesis in multiple myeloma. ‎Int J Cancer. 2009;124(6):1492-4. [DOI:10.1002/ijc.24110] [PMID]

23. Biggar RJ, Johansen JS, Smedby KE, Rostgaard K, Chang ET, Adami H-O, et al. Serum YKL-40 and interleukin 6 levels in Hodgkin lymphoma. Clin Cancer Res 2008;14(21):6974-8. [DOI:10.1158/1078-0432.CCR-08-1026] [PMID] [PMCID]

24. Mylin AK, Abildgaard N, Johansen JS, Heickendorff L, Kreiner S, Waage A, et al. Serum YKL-40: a new independent prognostic marker for skeletal complications in patients with multiple myeloma. Leuk Lymphoma. 2015;56(9):2650-9. [DOI:10.3109/10428194.2015.1004168] [PMID]

25. Cavo M, Rajkumar SV, Palumbo A, Moreau P, Orlowski R, Bladé J, et al. International Myeloma Working Group consensus approach to the treatment of multiple myeloma patients who are candidates for autologous stem cell transplantation. Blood. 2011;117(23):6063-73. [DOI:10.1182/blood-2011-02-297325] [PMID] [PMCID]

26. Kanoh T. Multiple myeloma: etiology, epidemiology, tumor biology and pathophysiology. Nihon Rinsho. 1995;53(3):543-51.

27. Pelloski CE, Mahajan A, Maor M, Chang EL, Woo S, Gilbert M, et al. YKL-40 expression is associated with poorer response to radiation and shorter overall survival in glioblastoma. Clin Cancer Res. 2005;11(9):3326-34. [DOI:10.1158/1078-0432.CCR-04-1765] [PMID]

28. Johansen JS, Schultz NA, Jensen BV. Plasma YKL-40: a potential new cancer biomarker? Future Oncol. 2009;5(7):1065-82. [DOI:10.2217/fon.09.66] [PMID]

29. Olfat SG, Yasser NH, Moataz KM, Ziad GS, Ahmed EM. Chitinase-3-Like Protein1 (YKL-40) as Biomarker in Serum of Egyptian Breast Cancer Females. Biochemistry and Analytical Biochemistry. 2014;3(2):1. [DOI:10.4172/2161-1009.1000149]

30. Guo Y, Xu F, Lu T, Duan Z, Zhang Z. Interleukin-6 signaling pathway in targeted therapy for cancer. Cancer Treat Rev. 2012;38(7):904-10. [DOI:10.1016/j.ctrv.2012.04.007] [PMID]

31. Kuku I, Bayraktar MR, Kaya E, Erkurt MA, Bayraktar N, Cıkım K, et al. Serum proinflammatory mediators at different periods of therapy in patients with multiple myeloma. Mediators Inflamm. 2005;2005(3):171-4. [DOI:10.1155/MI.2005.171] [PMID] [PMCID]

32. Terpos E, Viniou N, De La Fuente J, Meletis J, Voskaridou E, Karkantaris C, et al. Pamidronate is superior to ibandronate in decreasing bone resorption, interleukin‐6 and β2‐microglobulin in multiple myeloma. Eur J Haematol. 2003;70(1):34-42. [DOI:10.1034/j.1600-0609.2003.02823.x] [PMID]

33. Kaminska J, Koper OM, Dymicka-Piekarska V, Motybel E, Kloczko J, Kemona H. Angiogenic cytokines: IL-6, sIL-6R, TNF-α, sVCAM-1, and PDGF-AB in multiple myeloma patients depending on the stage of the disease. Edorium Journal of Tumor Biology. 2015;2:11-9.

34. Lee C, Oh J-I, Park J, Choi J-H, Bae E-K, Lee HJ, et al. TNFα mediated IL-6 secretion is regulated by JAK/STAT pathway but not by MEK phosphorylation and AKT phosphorylation in U266 multiple myeloma cells. Biomed Res Int. 2013;2013. [DOI:10.1155/2013/580135] [PMID] [PMCID]

35. Dalaveris E, Kerenidi T, Katsabeki-Katsafli A, Kiropoulos T, Tanou K, Gourgoulianis KI, et al. VEGF, TNF-α and 8-isoprostane levels in exhaled breath condensate and serum of patients with lung cancer. Lung Cancer. 2009;64(2):219-25 [DOI:10.1016/j.lungcan.2008.08.015] [PMID]