Correlation of Serum Levels of Interleukine-16, CCL27, Tumor Necrosis Factor-related Apoptosis-inducing Ligand, and B-cell Activating Factor with Multiple Sclerosis Severity
-
Ebrahim Kouchaki
,
Hossein Akbari
,
Fatemeh Mahmoudi
,
Mahdi Salehi
,
Effat Naimi
,
Hassan Nikoueinejad
Abstract
The pathogenic roles of Interleukine-16 (IL-16), CCL27, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and B-cell activating factor (BAFF) has been shown in some autoimmune and inflammatory diseases. We aimed to correlate the circulatory changes of such factors with the severity of disease in patients with multiple sclerosis (MS).
This case-control study was conducted on 84 MS patients and 83 healthy controls. We measured the serum levels of IL-16, CCL27, TRAIL, and BAFF in all participants by enzyme-linked immune sorbent assay. Using the expanded disability status scale (EDSS), we evaluated the severity of MS. Finally, we assessed the correlation between serum levels of such factors with the severity of MS.
We found increased serum levels of CCL27, IL-16, and BAFF in patients with MS compared to those in healthy subjects. However, no difference was found in serum levels of TRAIL between the patients and controls. In addition, a significant positive correlation between serum levels of CCL27, IL-16, TRAIL, and BAFF with disease severity according to EDSS score was determined.
We showed higher serum levels of CCL27, BAFF, TRAIL, and IL-16 in MS patients with more severe disabilities than mild forms. Such finding may represent their contribution to the pathogenesis of MS. Blocking such molecules may yield new treatments for MS.
1. Goldenberg MM. Multiple sclerosis review. PT. 2012;37(3):175-184.
2. Murray T. Diagnosis and treatment of multiple sclerosis. BMJ.2006;332(7540):525-527.
3. Etemadifar M, Maghzi A-H. Sharp increase in the incidence and prevalence of multiple sclerosis in Isfahan, Iran. Mul Scler.2011;17(8):1022-7.
4. Moghtaderi A, Rakhshanizadeh F, Shahraki-Ibrahimi S. Incidence and prevalence of multiple sclerosis in southeastern Iran. Clin neurol neurosurg. 2013;115(3):304-8.
5. Mikova O, Yakimova R, Bosmans E, Kenis G, Maes M. Increased serum tumor necrosis factor alpha concentrations in major depression and multiple sclerosis. Eur Neuropsychopharmacol.2001;11(3):203-8.
6. Kouchaki E, Tamtaji OR, Dadgostar E, Karami M, Nikoueinejad H, Akbari H. Correlation of Serum Levels of IL-33, IL-37, Soluble Form of Vascular Endothelial Growth Factor Receptor 2 (VEGFR2), and Circulatory Frequency of VEGFR2-expressing Cells with Multiple Sclerosis Severity. Iranian J AllergyAsthma Immunol.2017;16(4):329-337.
7. Akassoglou K, Bauer J, Kassiotis, M Pasparakis, H Lassmann, G Kollias, et al. Oligodendrocyte apoptosis and primary demyelination induced by local TNF/p55TNF receptor signaling in the central nervous system of transgenic mice: models for multiple sclerosis with primary oligodendrogliopathy. Am J Pathol. 1998;153(3):801-13.
8. Baier M, Bannert N, Werner A, Lang K, Kurth R. Molecular cloning, sequence, expression, and processing of the interleukin 16 precursor. Proc Natl Acad Sci U S A. 1997;94(10):5273-7.
9. Laberge S, Cruikshank WW, Kornfeld H, Center DM. Histamine-induced secretion of lymphocyte chemoattractant factor from CD8+ T cells is independent of transcription and translation. Evidence for constitutive protein synthesis and storage. J Immunol. 1995;155(6):2902-10.
10. Cruikshank WW, Center DM, Nisar N, M Wu, B Natke, AC Theodore,et al. Molecular and functional analysis of a lymphocyte chemoattractant factor: association of biologic function with CD4 expression. Proc Natl AcadSci U S A. 1994;91(11):5109-13.
11. Sharma V, Sparks J, Vail J. Human B‐cell lines constitutively express and secrete interleukin‐16. Immunology. 2000;99(2):266-71.
12. Zhang Y, Center DM, David M, WW Cruikshank, J Yuan, DW Andrews,et al. Processing and activation of pro-interleukin-16 by caspase-3. JBiol Chem. 1998;273(2):1144-9.
13. Mathy N, Scheuer W, Lanzendörfer M, K Honold, D Ambrosius, S Norley, et al. Interleukin‐16 stimulates the expression and production of pro‐inflammatory cytokines by human monocytes. Immunology. 2000;100(1):63-9.
14. Laberge S, Ernst P, Ghaffar O, WW Cruikshank, H Kornfeld, DM Center,et al. Increased expression of interleukin-16 in bronchial mucosa of subjects with atopic asthma. Am J Respir Cell Mol Biol. 1997;17(2):193-202.
15. Lynch EA, Heijens CA, Horst NF, Center DM, Cruikshank WW. Cutting edge: IL-16/CD4 preferentially induces Th1 cell migration: requirement of CCR5. J Immunol. 2003;171(10):4965-8.
16. Schwab J, Schluesener H, Seid K, Meyermann R. IL-16 is differentially expressed in the developing human fetal brain by microglial cells in zones of neuropoesis. Int J Dev Neurosci. 2001;19(1):93-100.
17. Guo L-H, Mittelbronn M, Brabeck C, Mueller CA, Schluesener HJ. Expression of interleukin-16 by microglial cells in inflammatory, autoimmune, and degenerative lesions of the rat brain. Neuroimmunol. 2004;146(1-2):39-45.
18. Liebrich M, Guo L-H, Schluesener HJ, Jan M Schwab, Klaus Dietz, Bernd E Will, et al. Expression of interleukin-16 by tumor-associated macrophages/activated microglia in high-grade astrocytic brain tumors. Arc Immunol Ther Exp. 2007;55(1):41-7.
19. Abbott NJ, Rönnbäck L, Hansson E. Astrocyte–endothelial interactions at the blood–brain barrier. Nat Rev Neurosci. 2006;7(1):41-53.
20. Homey B, Wang W, Soto H, M E Buchanan, A Wiesenborn, D Catron, et al. Cutting edge: the orphan chemokine receptor G protein-coupled receptor-2 (GPR-2, CCR10) binds the skin-associated chemokine CCL27 (CTACK/ALP/ILC). J Immunol. 2000;164(7):3465-70.
21. Homey B, Alenius H, Müller A, Hortensia Soto, Edward P Bowman, Wei Yuan, et al. CCL27–CCR10 interactions regulate T cell–mediated skin inflammation. Nat Med. 2002;8(2):157-65.
22. Cartier L, Hartley O, Dubois-Dauphin M, Krause K-H. Chemokine receptors in the central nervous system: role in brain inflammation and neurodegenerative diseases. Brain Res Rev. 2005;48(1):16-42.
23. Williams JL, Holman DW, Klein RS. Chemokines in the balance: maintenance of homeostasis and protection at CNS barriers. Front Cell Neurosci. 2014;8:154.
24. Wueest S, Rapold RA, Schumann DM. Deletion of Fas in adipocytes relieves adipose tissue inflammation and hepatic manifestations of obesity in mice. J Clin Invest. 2010;120(12):191–202.
25. Zoller V, Funcke JB, Roos J. Trail (TNF-related apoptosis-inducing ligand) induces an inflammatory response in human adipocytes. Sci Rep. 2017;7(1):5691.
26. Bodmer J-L, Schneider P, Tschopp J. The molecular architecture of the TNF superfamily. Trends Biochem Sci. 2002;27(5):19–26.
27. Cui M, Wang L, Liang X,Xuelian Ma, Yugang Liu, Mingfeng Yang,et al. Blocking TRAIL-DR5 signaling with soluble DR5 reduces delayed neuronal damage after transient global cerebral ischemia. Neurobiol Dis.2010;39(2):138–47.
28. Krajewska M, You Z, Rong J, Christina Kress, Xianshu Huang, Jinsheng Yang, et al. Neuronal deletion of caspase 8 protects against brain injury in mouse models of controlled cortical impact and kainic acid-induced excitotoxicity. PLoS One. 2011;6(9),e24341.
29. Clarke P, Leser JS, Quick ED, Dionne KR, Beckham JD, Tyler KL. Death receptor mediated apoptotic signaling is activated in the brain following infection with West Nile virus in the absence of a peripheral immune response. J Virol. 2014;88(5):1080–9.
30. Cannella B, Gaupp S, Omari KM, Raine CS. Multiple sclerosis: death receptor expression and oligodendrocyte apoptosis in established lesions. J Neuroimmunol. 2007;188(12):128–37.
31. Mc Guire C, Beyaert R, van Loo G. Death receptor signalling in central nervous system inflammation and demyelination. Trends Neurosci. 2011;34(8):619–28.
32. Groom J, Kalled SL, Cutler AH, et al. Association of BAFF/BLyS overexpression and altered B cell differentiation with Sjogren’s syndrome. J Clin Invest. 2002;109(14):59–68.
33. Cheema GS, Roschke V, Hilbert DM, Stohl W. Elevated serum B lymphocyte stimulator levels in patients with systemic immune-based rheumatic diseases. Arthritis Rheum. 2001;44:1313–9.
34. Mackay F, Woodcock SA, Lawton P, et al. Mice transgenic for BAFF develop lymphocytic disorders along with autoimmune manifestations. J Exp Med. 1999;190(23):1697–710.
35. Ragheb S, Li Y, Simon K, et al. Multiple sclerosis: BAFF and CXCL13 in cerebrospinal fluid. Mult Scler. 2011,17(7):819-29.
36. Nischwitz S, Faber H, Sämann P, et al. Interferon β‐1a reduces increased interleukin‐16 levels in multiple sclerosis patients. Acta Neurol Scand. 2014;130(1):46-52.
37. Skundric DS, Cai J, Cruikshank WW, Gveric D. Production of IL-16 correlates with CD4+ Th1 inflammation and phosphorylation of axonal cytoskeleton in multiple sclerosis lesions. J Neuroinflammation. 2006;3(1):13-9.
38. Skundric DS, Zhou W, Cruikshank WW, Dai R. Increased levels of bioactive IL-16 correlate with disease activity during relapsing experimental autoimmune encephalomyelitis (EAE). J Autoimmun. 2005;25(3):206-14.
39. Bakr NM, Hashim NA, Alaa El-Din El-Baz H, Khalaf EM, Elharoun AS. Polymorphisms in proinflammatory cytokines genes and susceptibility to Multiple Sclerosis. Mult Scler Relat Disord. 2021;47:102654.
40. Benoit M, Fenollar F, Raoult D, Mege J-L. Increased levels of circulating IL-16 and apoptosis markers are related to the activity of Whipple's disease. PloS one. 2007;2(6):e494.
41. Khaiboullina SF, Gumerova AR, Khafizova IF, Ekaterina V Martynova, Vincent C Lombardi, Saverio Bellusci. CCL27: novel cytokine with potential role in pathogenesis of multiple sclerosis. BioMed Res Int. 2015;2015:189638.
42. Kurne A, Guc D, Canpinar H, M Yörübulut, G Esendagli, R Karabudak. Analysis of BAFF and TRAIL expression levels in multiple sclerosis patients: evaluation of expression under immunomodulatory therapy. Acta Neurol Scand. 2011;123(1):8-12.
43. Dooley J, Pauwels I, Franckaert D, et al. Immunologic profiles of multiple sclerosis treatments reveal shared early B cell alterations. Neurol Neuroimmunol Neuroinflamm. 2016;3(4):e240.
44. MacKay F, Woodcock SA, Lawton P. Mice transgenic for BAFF develop lymphocytic disorders along with autoimmune manifestations. J Exp Med. 1999;190:1697–710.
45. Kalled SL. The role of BAFF in immune function and implications for autoimmunity. Immunol Rev. 2005;204(12):43–54.
46. Lesley R, Xu Y, Kalled SL. Reduced competitiveness of autoantigen-engaged B cells due to increased dependence on BAFF. Immunity. 2004;20:441–53.
47. Wang H1, Wang K, Zhong X, Qiu W, Dai Y, Wu A, Hu X.Cerebrospinal fluid BAFF and APRIL levels in neuromyelitis optica and multiple sclerosis patients during relapse. J Clin Immunol. 2012;32(5):1007-11.
2. Murray T. Diagnosis and treatment of multiple sclerosis. BMJ.2006;332(7540):525-527.
3. Etemadifar M, Maghzi A-H. Sharp increase in the incidence and prevalence of multiple sclerosis in Isfahan, Iran. Mul Scler.2011;17(8):1022-7.
4. Moghtaderi A, Rakhshanizadeh F, Shahraki-Ibrahimi S. Incidence and prevalence of multiple sclerosis in southeastern Iran. Clin neurol neurosurg. 2013;115(3):304-8.
5. Mikova O, Yakimova R, Bosmans E, Kenis G, Maes M. Increased serum tumor necrosis factor alpha concentrations in major depression and multiple sclerosis. Eur Neuropsychopharmacol.2001;11(3):203-8.
6. Kouchaki E, Tamtaji OR, Dadgostar E, Karami M, Nikoueinejad H, Akbari H. Correlation of Serum Levels of IL-33, IL-37, Soluble Form of Vascular Endothelial Growth Factor Receptor 2 (VEGFR2), and Circulatory Frequency of VEGFR2-expressing Cells with Multiple Sclerosis Severity. Iranian J AllergyAsthma Immunol.2017;16(4):329-337.
7. Akassoglou K, Bauer J, Kassiotis, M Pasparakis, H Lassmann, G Kollias, et al. Oligodendrocyte apoptosis and primary demyelination induced by local TNF/p55TNF receptor signaling in the central nervous system of transgenic mice: models for multiple sclerosis with primary oligodendrogliopathy. Am J Pathol. 1998;153(3):801-13.
8. Baier M, Bannert N, Werner A, Lang K, Kurth R. Molecular cloning, sequence, expression, and processing of the interleukin 16 precursor. Proc Natl Acad Sci U S A. 1997;94(10):5273-7.
9. Laberge S, Cruikshank WW, Kornfeld H, Center DM. Histamine-induced secretion of lymphocyte chemoattractant factor from CD8+ T cells is independent of transcription and translation. Evidence for constitutive protein synthesis and storage. J Immunol. 1995;155(6):2902-10.
10. Cruikshank WW, Center DM, Nisar N, M Wu, B Natke, AC Theodore,et al. Molecular and functional analysis of a lymphocyte chemoattractant factor: association of biologic function with CD4 expression. Proc Natl AcadSci U S A. 1994;91(11):5109-13.
11. Sharma V, Sparks J, Vail J. Human B‐cell lines constitutively express and secrete interleukin‐16. Immunology. 2000;99(2):266-71.
12. Zhang Y, Center DM, David M, WW Cruikshank, J Yuan, DW Andrews,et al. Processing and activation of pro-interleukin-16 by caspase-3. JBiol Chem. 1998;273(2):1144-9.
13. Mathy N, Scheuer W, Lanzendörfer M, K Honold, D Ambrosius, S Norley, et al. Interleukin‐16 stimulates the expression and production of pro‐inflammatory cytokines by human monocytes. Immunology. 2000;100(1):63-9.
14. Laberge S, Ernst P, Ghaffar O, WW Cruikshank, H Kornfeld, DM Center,et al. Increased expression of interleukin-16 in bronchial mucosa of subjects with atopic asthma. Am J Respir Cell Mol Biol. 1997;17(2):193-202.
15. Lynch EA, Heijens CA, Horst NF, Center DM, Cruikshank WW. Cutting edge: IL-16/CD4 preferentially induces Th1 cell migration: requirement of CCR5. J Immunol. 2003;171(10):4965-8.
16. Schwab J, Schluesener H, Seid K, Meyermann R. IL-16 is differentially expressed in the developing human fetal brain by microglial cells in zones of neuropoesis. Int J Dev Neurosci. 2001;19(1):93-100.
17. Guo L-H, Mittelbronn M, Brabeck C, Mueller CA, Schluesener HJ. Expression of interleukin-16 by microglial cells in inflammatory, autoimmune, and degenerative lesions of the rat brain. Neuroimmunol. 2004;146(1-2):39-45.
18. Liebrich M, Guo L-H, Schluesener HJ, Jan M Schwab, Klaus Dietz, Bernd E Will, et al. Expression of interleukin-16 by tumor-associated macrophages/activated microglia in high-grade astrocytic brain tumors. Arc Immunol Ther Exp. 2007;55(1):41-7.
19. Abbott NJ, Rönnbäck L, Hansson E. Astrocyte–endothelial interactions at the blood–brain barrier. Nat Rev Neurosci. 2006;7(1):41-53.
20. Homey B, Wang W, Soto H, M E Buchanan, A Wiesenborn, D Catron, et al. Cutting edge: the orphan chemokine receptor G protein-coupled receptor-2 (GPR-2, CCR10) binds the skin-associated chemokine CCL27 (CTACK/ALP/ILC). J Immunol. 2000;164(7):3465-70.
21. Homey B, Alenius H, Müller A, Hortensia Soto, Edward P Bowman, Wei Yuan, et al. CCL27–CCR10 interactions regulate T cell–mediated skin inflammation. Nat Med. 2002;8(2):157-65.
22. Cartier L, Hartley O, Dubois-Dauphin M, Krause K-H. Chemokine receptors in the central nervous system: role in brain inflammation and neurodegenerative diseases. Brain Res Rev. 2005;48(1):16-42.
23. Williams JL, Holman DW, Klein RS. Chemokines in the balance: maintenance of homeostasis and protection at CNS barriers. Front Cell Neurosci. 2014;8:154.
24. Wueest S, Rapold RA, Schumann DM. Deletion of Fas in adipocytes relieves adipose tissue inflammation and hepatic manifestations of obesity in mice. J Clin Invest. 2010;120(12):191–202.
25. Zoller V, Funcke JB, Roos J. Trail (TNF-related apoptosis-inducing ligand) induces an inflammatory response in human adipocytes. Sci Rep. 2017;7(1):5691.
26. Bodmer J-L, Schneider P, Tschopp J. The molecular architecture of the TNF superfamily. Trends Biochem Sci. 2002;27(5):19–26.
27. Cui M, Wang L, Liang X,Xuelian Ma, Yugang Liu, Mingfeng Yang,et al. Blocking TRAIL-DR5 signaling with soluble DR5 reduces delayed neuronal damage after transient global cerebral ischemia. Neurobiol Dis.2010;39(2):138–47.
28. Krajewska M, You Z, Rong J, Christina Kress, Xianshu Huang, Jinsheng Yang, et al. Neuronal deletion of caspase 8 protects against brain injury in mouse models of controlled cortical impact and kainic acid-induced excitotoxicity. PLoS One. 2011;6(9),e24341.
29. Clarke P, Leser JS, Quick ED, Dionne KR, Beckham JD, Tyler KL. Death receptor mediated apoptotic signaling is activated in the brain following infection with West Nile virus in the absence of a peripheral immune response. J Virol. 2014;88(5):1080–9.
30. Cannella B, Gaupp S, Omari KM, Raine CS. Multiple sclerosis: death receptor expression and oligodendrocyte apoptosis in established lesions. J Neuroimmunol. 2007;188(12):128–37.
31. Mc Guire C, Beyaert R, van Loo G. Death receptor signalling in central nervous system inflammation and demyelination. Trends Neurosci. 2011;34(8):619–28.
32. Groom J, Kalled SL, Cutler AH, et al. Association of BAFF/BLyS overexpression and altered B cell differentiation with Sjogren’s syndrome. J Clin Invest. 2002;109(14):59–68.
33. Cheema GS, Roschke V, Hilbert DM, Stohl W. Elevated serum B lymphocyte stimulator levels in patients with systemic immune-based rheumatic diseases. Arthritis Rheum. 2001;44:1313–9.
34. Mackay F, Woodcock SA, Lawton P, et al. Mice transgenic for BAFF develop lymphocytic disorders along with autoimmune manifestations. J Exp Med. 1999;190(23):1697–710.
35. Ragheb S, Li Y, Simon K, et al. Multiple sclerosis: BAFF and CXCL13 in cerebrospinal fluid. Mult Scler. 2011,17(7):819-29.
36. Nischwitz S, Faber H, Sämann P, et al. Interferon β‐1a reduces increased interleukin‐16 levels in multiple sclerosis patients. Acta Neurol Scand. 2014;130(1):46-52.
37. Skundric DS, Cai J, Cruikshank WW, Gveric D. Production of IL-16 correlates with CD4+ Th1 inflammation and phosphorylation of axonal cytoskeleton in multiple sclerosis lesions. J Neuroinflammation. 2006;3(1):13-9.
38. Skundric DS, Zhou W, Cruikshank WW, Dai R. Increased levels of bioactive IL-16 correlate with disease activity during relapsing experimental autoimmune encephalomyelitis (EAE). J Autoimmun. 2005;25(3):206-14.
39. Bakr NM, Hashim NA, Alaa El-Din El-Baz H, Khalaf EM, Elharoun AS. Polymorphisms in proinflammatory cytokines genes and susceptibility to Multiple Sclerosis. Mult Scler Relat Disord. 2021;47:102654.
40. Benoit M, Fenollar F, Raoult D, Mege J-L. Increased levels of circulating IL-16 and apoptosis markers are related to the activity of Whipple's disease. PloS one. 2007;2(6):e494.
41. Khaiboullina SF, Gumerova AR, Khafizova IF, Ekaterina V Martynova, Vincent C Lombardi, Saverio Bellusci. CCL27: novel cytokine with potential role in pathogenesis of multiple sclerosis. BioMed Res Int. 2015;2015:189638.
42. Kurne A, Guc D, Canpinar H, M Yörübulut, G Esendagli, R Karabudak. Analysis of BAFF and TRAIL expression levels in multiple sclerosis patients: evaluation of expression under immunomodulatory therapy. Acta Neurol Scand. 2011;123(1):8-12.
43. Dooley J, Pauwels I, Franckaert D, et al. Immunologic profiles of multiple sclerosis treatments reveal shared early B cell alterations. Neurol Neuroimmunol Neuroinflamm. 2016;3(4):e240.
44. MacKay F, Woodcock SA, Lawton P. Mice transgenic for BAFF develop lymphocytic disorders along with autoimmune manifestations. J Exp Med. 1999;190:1697–710.
45. Kalled SL. The role of BAFF in immune function and implications for autoimmunity. Immunol Rev. 2005;204(12):43–54.
46. Lesley R, Xu Y, Kalled SL. Reduced competitiveness of autoantigen-engaged B cells due to increased dependence on BAFF. Immunity. 2004;20:441–53.
47. Wang H1, Wang K, Zhong X, Qiu W, Dai Y, Wu A, Hu X.Cerebrospinal fluid BAFF and APRIL levels in neuromyelitis optica and multiple sclerosis patients during relapse. J Clin Immunol. 2012;32(5):1007-11.
| Files | ||
| Issue | Vol 21 No 1 (2022) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v21i1.8610 | |
| Keywords | ||
| B cell-activating factor Chemokine CCL27 Multiple sclerosis TNF-related apoptosis-inducing ligand | ||
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How to Cite
1.
Kouchaki E, Akbari H, Mahmoudi F, Salehi M, Naimi E, Nikoueinejad H. Correlation of Serum Levels of Interleukine-16, CCL27, Tumor Necrosis Factor-related Apoptosis-inducing Ligand, and B-cell Activating Factor with Multiple Sclerosis Severity. Iran J Allergy Asthma Immunol. 2022;21(1):27-34.
