Volume 10, Issue 2 (Vol.10 No.2 Jul 2021)                   rbmb.net 2021, 10(2): 216-223 | Back to browse issues page

XML Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Asadzadeh R, Ahmadpoor P, Nafar M, Samavat S, Nikoueinejad H, Hosseinzadeh M, et al . Association of IL-15 and IP-10 Serum Levels with Cytomegalovirus Infection, CMV Viral Load and Cyclosporine Level after Kidney Transplantation. rbmb.net. 2021; 10 (2) :216-223
URL: http://rbmb.net/article-1-633-en.html
Urology and Nephrology Research Center, Shahid Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Abstract:   (756 Views)
Background: Cytomegalovirus (CMV) infection is the most common complications following kidney transplantation. Natural killer (NK) cells demonstrated critical anti-viral role in controlling and elimination of CMV after transplantation. Interleukin-15 (IL-15) is a pleiotropic cytokine that promotes the activity of NK cells and strengthens the acquired immune system. Also, IP10 (CXCL10) is a chemotactic factor which regulates NK cell recruitment and antiviral immune response. We aimed to determine the correlation between the serum levels of IL-15 and IP-10 cytokines with CMV infection, CMV viral load, and cyclosporine as a major immunosuppressive treatment after transplantation.

Methods: Fifty-eight kidney transplant recipient patients without evidence of CMV virus disease before transplantation surgery were included in the study. From the day of transplant surgery, the patients were evaluated based on the presence of CMV Ag pp65, CMV viral load, serum levels of IL-15 & IP-10, Cyclosporine levels (C0 & C2), Glomerular Filtration Rate (GFR), and hematological & biochemical Index, up to 75 days.

Results: Comparison analysis of serum levels of IL-15 and IP-10 showed no significant association with CMV infection in kidney transplant recipients. In addition, CMV viral load and cyclosporine levels at C0 and C2 did not affect patients' IL-15 and IP-10 levels.

Conclusions: The levels of IP-10 and IL-15 cytokines are not affected with CMV infection, even if a viral infection occurs in the early days after transplantation or long afterwards. In addition, taking the different levels of cyclosporine did not affect the cytokines levels. Other mechanisms may play a role in maintaining the levels of these cytokines.
Full-Text [PDF 205 kb]   (362 Downloads)    
Type of Article: Original Article | Subject: Immunology
Received: 2021/01/5 | Accepted: 2021/03/8 | Published: 2021/08/26

1. Kotton CN, Fishman JA. Viral infection in the renal transplant recipient. J Am Soc Nephrol. 2005;16(6):1758-74. [DOI:10.1681/ASN.2004121113] [PMID]
2. Meyers JD, Flournoy N, Donnall Thomas E. Risk factors for cytomegalovirus infection after human marrow transplantation. Risk factors for cytomegalovirus infection after human marrow transplantation. 1986;153(3):478-88. [DOI:10.1093/infdis/153.3.478] [PMID]
3. Mattes F, Vargas A, Kopycinski J, Hainsworth E, Sweny P, Nebbia G, et al. Functional impairment of cytomegalovirus specific CD8 T cells predicts high‐level replication after renal transplantation. Am J Transplant. 2008;8(5):990-9. [DOI:10.1111/j.1600-6143.2008.02191.x] [PMID]
4. Davis ZB, Cooley SA, Cichocki F, Felices M, Wangen R, Luo X, et al. Adaptive natural killer cell and killer cell immunoglobulin-like receptor-expressing T cell responses are induced by cytomegalovirus and are associated with protection against cytomegalovirus reactivation after allogeneic donor hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2015;21(9):1653-62. [DOI:10.1016/j.bbmt.2015.05.025] [PMID] [PMCID]
5. Gangappa S, Kokko KE, Carlson LM, Gourley T, Newell KA, Pearson TC, et al. Immune responsiveness and protective immunity after transplantation. Transpl Int. 2008;21(4):293-303. [DOI:10.1111/j.1432-2277.2007.00631.x] [PMID]
6. Yap M, Boeffard F, Clave E, Pallier A, Danger R, Giral M, et al. Expansion of highly differentiated cytotoxic terminally differentiated effector memory CD8+ T cells in a subset of clinically stable kidney transplant recipients: a potential marker for late graft dysfunction. J Am Soc Nephrol. 2014;25(8):1856-68. [DOI:10.1681/ASN.2013080848] [PMID] [PMCID]
7. Neudoerfl C, Mueller BJ, Blume C, Daemen K, Stevanovic-Meyer M, Keil J, et al. The peripheral NK cell repertoire after kidney transplantation is modulated by different immunosuppressive drugs. Front Immunol. 2013;4:46. [DOI:10.3389/fimmu.2013.00046] [PMID] [PMCID]
8. DeWolfe D, Aid M, McGann K, Ghofrani J, Geiger E, Helzer C, et al. NK cell contributes to the immune risk profile in kidney transplant candidates. Front Immunol. 2019;10:1890. [DOI:10.3389/fimmu.2019.01890] [PMID] [PMCID]
9. Poli A, Michel T, Thérésine M, Andrès E, Hentges F, Zimmer J. CD56bright natural killer (NK) cells: an important NK cell subset. Immunology. 2009;126(4):458-65. [DOI:10.1111/j.1365-2567.2008.03027.x] [PMID] [PMCID]
10. Sun JC, Lanier LL. NK cell development, homeostasis and function: parallels with CD8+ T cells. Nat Rev Immunol. 2011;11(10):645-57. [DOI:10.1038/nri3044] [PMID] [PMCID]
11. Nandagopal N, Ali AK, Komal AK, Lee S-H. The critical role of IL-15-PI3K-mTOR pathway in natural killer cell effector functions. Front Immunol. 2014;5:187. [DOI:10.3389/fimmu.2014.00187] [PMID] [PMCID]
12. Lauwerys BR, Garot N, Renauld J-C, Houssiau FA. Cytokine production and killer activity of NK/T-NK cells derived with IL-2, IL-15, or the combination of IL-12 and IL-18. J Immunol. 2000;165(4):1847-53. [DOI:10.4049/jimmunol.165.4.1847] [PMID]
13. Zanoni I, Spreafico R, Bodio C, Di Gioia M, Cigni C, Broggi A, et al. IL-15 cis presentation is required for optimal NK cell activation in lipopolysaccharide-mediated inflammatory conditions. Cell Rep. 2013;4(6):1235-49. [DOI:10.1016/j.celrep.2013.08.021] [PMID]
14. Carson WE, Giri JG, Lindemann M, Linett ML, Ahdieh M, Paxton R, et al. Interleukin (IL) 15 is a novel cytokine that activates human natural killer cells via components of the IL-2 receptor. J Exp Med. 1994;180(4):1395-403. [DOI:10.1084/jem.180.4.1395] [PMID] [PMCID]
15. Rettinger E, Huenecke S, Bonig H, Merker M, Jarisch A, Soerensen J, et al. Interleukin-15-activated cytokine-induced killer cells may sustain remission in leukemia patients after allogeneic stem cell transplantation: feasibility, safety and first insights on efficacy. Haematologica. 2016;101(4):e153-e156. [DOI:10.3324/haematol.2015.138016] [PMID] [PMCID]
16. Booth V, Keizer DW, Kamphuis MB, Clark-Lewis I, Sykes BD. The CXCR3 binding chemokine IP-10/CXCL10: structure and receptor interactions. Biochemistry. 2002;41(33):10418-25. [DOI:10.1021/bi026020q] [PMID]
17. Liu M, Guo S, Stiles JK. The emerging role of CXCL10 in cancer. Oncol Lett . 2011;2(4):583-589. [DOI:10.3892/ol.2011.300] [PMID] [PMCID]
18. Lee EY, Lee Z-H, Song YW. CXCL10 and autoimmune diseases. Autoimmun Rev. 2009;8(5):379-83. [DOI:10.1016/j.autrev.2008.12.002] [PMID]
19. Bai X, Wilson SE, Chmura K, Feldman NE, Chan ED. Morphometric analysis of Th1 and Th2 cytokine expression in human pulmonary tuberculosis. Tuberculosis (Edinb). 2004;84(6):375-85. [DOI:10.1016/j.tube.2004.05.001] [PMID]
20. Romero AI, Lagging M, Westin J, Dhillon AP, Dustin LB, Pawlotsky JM, et al. Interferon (IFN)- gamma-inducible protein-10: association with histological results, viral kinetics, and outcome during treatment with pegylated IFN-alpha 2a and ribavirin for chronic hepatitis C virus infection. The Journal of infectious diseases. 2006;194(7):895-903. [DOI:10.1086/507307] [PMID]
21. Weseslindtner L, Nachbagauer R, Kundi M, Jaksch P, Kerschner H, Simon B, et al. Human cytomegalovirus infection in lung transplant recipients triggers a CXCL‐10 response. Am J Transplant. 2011;11(3):542-52. [DOI:10.1111/j.1600-6143.2010.03404.x] [PMID]
22. Husain S, Resende MR, Rajwans N, Zamel R, Pilewski JM, Crespo MM, et al. Elevated CXCL10 (IP-10) in bronchoalveolar lavage fluid is associated with acute cellular rejection after human lung transplantation. Transplantation. 2014;97(1):90-7. [DOI:10.1097/TP.0b013e3182a6ee0a] [PMID] [PMCID]
23. Barakat O, Peaston R, Rai R, Talbot D, Manas D. Clinical benefit of monitoring cyclosporine C2 and C4 in long-term liver transplant recipients. Transplant Proc. 2002;34(5):1535-7. [DOI:10.1016/S0041-1345(02)03009-9]
24. Cukuranovic J, Ugrenovic S, Jovanovic I, Visnjic M, Stefanovic V. Viral infection in renal transplant recipients. Scientific World Journal. 2012;2012:820621. [DOI:10.1100/2012/820621] [PMID] [PMCID]
25. Mao Y, van Hoef V, Zhang X, Wennerberg E, Lorent J, Witt K, et al. IL-15 activates mTOR and primes stress-activated gene expression leading to prolonged antitumor capacity of NK cells. Blood. 2016;128(11):1475-89. [DOI:10.1182/blood-2016-02-698027] [PMID] [PMCID]
26. Taub DD, Sayers TJ, Carter C, Ortaldo JR. Alpha and beta chemokines induce NK cell migration and enhance NK-mediated cytolysis. J Immunol. 1995;155(8):3877-88.
27. Parkes MD, Halloran PF, Hidalgo LG. Evidence for CD16a-mediated NK cell stimulation in antibody-mediated kidney transplant rejection. Transplantation. 2017;101(4):e102-e111. [DOI:10.1097/TP.0000000000001586] [PMID] [PMCID]
28. Eissens DN, Van Der Meer A, Van Cranenbroek B, Preijers F, Joosten I. Rapamycin and MPA, but not CsA, impair human NK cell cytotoxicity due to differential effects on NK cell phenotype. Am J Transplant. 2010;10(9):1981-90. [DOI:10.1111/j.1600-6143.2010.03242.x] [PMID]
29. Ohata K, Espinoza JL, Lu X, Kondo Y, Nakao S. Mycophenolic acid inhibits natural killer cell proliferation and cytotoxic function: a possible disadvantage of including mycophenolate mofetil in the graft-versus-host disease prophylaxis regimen. Biol Blood Marrow Transplant. 2011;17(2):205-13. [DOI:10.1016/j.bbmt.2010.08.014] [PMID]
30. Husain S, Resende MR, Rajwans N, Zamel R, Pilewski JM, Crespo MM, et al. Elevated CXCL10 (IP-10) in bronchoalveolar lavage fluid is associated with acute cellular rejection after human lung transplantation. Transplantation. 2014;97(1):90-7. [DOI:10.1097/TP.0b013e3182a6ee0a] [PMID] [PMCID]
31. Alpdogan O, Eng JM, Muriglan SJ, Willis LM, Hubbard VM, Tjoe KH, et al. Interleukin-15 enhances immune reconstitution after allogeneic bone marrow transplantation. Blood. 2005;105(2):865-73. [DOI:10.1182/blood-2003-09-3344] [PMID]
32. Lin S, Kuo M. Effect of cyclosporin A on interleukin-15-activated umbilical cord blood natural killer cell function. Cytotherapy. 2008;10(4):397-405. [DOI:10.1080/14653240802129885] [PMID]
33. Bekiaris V, Timoshenko O, Hou TZ, Toellner K, Shakib S, Gaspal F, et al. Ly49H+ NK cells migrate to and protect splenic white pulp stroma from murine cytomegalovirus infection. J Immunol. 2008;180(10):6768-76. [DOI:10.4049/jimmunol.180.10.6768] [PMID]

Add your comments about this article : Your username or Email:

Send email to the article author

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

© 2015 All Rights Reserved | Reports of Biochemistry and Molecular Biology

Designed & Developed by : Yektaweb