Iranian Journal of Allergy, Asthma and Immunology 2017. 16(4):347-357.

Polarization of Helper T Lymphocytes May Be Involved in the Pathogenesis of Lumbar Disc Herniation
Yu Yao, Huawei Xue, Xiangdong Chen, Yong Cao, Jiang Yu, Xingjie Jiang, Feng Zhang

Abstract


This study aimed to explore the expression of T helper type 1 (Th1)/T helper type 2 (Th2) in herniated nucleus pulposus (NP) and determine their association with sciatic pain. NP was collected from 12 patients with lumbar disc herniation (LDH) (extrusion group) and 6 patients with a vertebral fracture (control group). The expression of Th1/Th2 and related cytokines in the NP was examined by flow cytometry, Western blot, and immunofluorescent staining. Subsequently, an LDH model was established in male Sprague–Dawley rats, and behavioral testings were carried out. The expression of Th1/Th2 and related cytokines in rat NP and the expression of macrophages in the dorsal root ganglia (DRG) were also examined. The number of Th1 cells in rat NP dramatically increased on day 14 after the surgery, but significantly decreased on day 28. The number of Th2 cells increased on day 28. Chemokine ligand 3(CCL3) and CD86 proteins (M1-specific molecules) were expressed at a relatively low level in naive DRG, markedly increased on day 14 after the surgery, and decreased on day 28. Arg1 and CD206 protein (M2-specific molecules) were expressed at a relatively low level in naive DRG and markedly increased on day 28. The mechanical allodynia and heat hyperalgesia developed after NP application and finally partially alleviated. The results suggested that the polarization of Th cells might be involved in the pathogenesis of LDH, and this might be achieved via the phenotypic shift of macrophages.


Keywords


Lumbar disc herniation; Macrophages; T helper type 1 (Th1); T helper type 2 (Th2)

Full Text:

PDF

References


[1] Wiesel SW, Tsourmas N, Feffer HL, Citrin CM, Patronas N. A study of computer-assisted tomography. I. The incidence of positive CAT scans in an asymptomatic group of patients. Spine (Phila Pa 1976). 1984 Sep;9(6):549-51. PubMed PMID: 6495024.

[2] Macnab I. Cervical spondylosis. Clin Orthop Relat Res. 1975;(109):69-77.PubMed PMID: 1132207.

[3] Naylor A, Happey F, Turner RL, Shentall RD, West DC, Richardson C. Enzymic and immunological activity in the intervertebral disk. Orthop Clin North Am. 1975 Jan;6(1):51-8. PubMed PMID: 1113980.

[4] Kobayashi S, Meir A, Kokubo Y, Uchida K, Takeno K, Miyazaki T, Yayama T, Kubota M, Nomura E, Mwaka E, Baba H. Ultrastructural analysis on lumbar disc herniation using surgical specimens: role of neovascularization and macrophages in hernias. Spine (Phila Pa 1976). 2009 Apr 1;34(7):655-62. doi: 10.1097/BRS.0b013e31819c9d5b. PubMed PMID: 19333096.

[5]Cheng L, Fan W, Liu B, Wang X, Nie L. Th17 lymphocyte levels are higher in patients with ruptured than non-ruptured lumbar discs, and are correlated with pain intensity. Injury. 2013 Dec;44(12):1805-10. doi:10.1016/j.injury.2013.04.010. Epub 2013 May 13. PubMed PMID: 23680281.

[6] Kepler CK, Markova DZ, Dibra F, Yadla S, Vaccaro AR, Risbud MV, Albert TJ,Anderson DG. Expression and relationship of proinflammatory chemokine RANTES/CCL5 and cytokine IL-1β in painful human intervertebral discs. Spine (Phila Pa 1976). 2013 May 15;38(11):873-80. doi: 10.1097/BRS.0b013e318285ae08. PubMed PMID:23660804.

[7] Kraychete DC, Sakata RK, Issy AM, Bacellar O, Santos-Jesus R, Carvalho EM. Serum cytokine levels in patients with chronic low back pain due to herniated disc: analytical cross-sectional study. Sao Paulo Med J. 2010;128(5):259-62. PubMed PMID: 21181064.

[8] Xue H, Yao Y, Wang X, Zhang F, Jiang X, Liu J, Wang H, Li Y, Wang X, Li H, Zhang J. Interleukin-21 Is Associated with the Pathogenesis of Lumbar Disc Herniation. Iran J Allergy Asthma Immunol. 2015 Oct;14(5):509-18. PubMed PMID:26742440.

[9] Saal JS, Franson RC, Dobrow R, Saal JA, White AH, Goldthwaite N. High levels of inflammatory phospholipase A2 activity in lumbar disc herniations. Spine (Phila Pa 1976). 1990 Jul;15(7):674-8. PubMed PMID: 2218714.

[10]Heilmann RM, Suchodolski JS. Is inflammatory bowel disease in dogs and cats associated with a Th1 or Th2 polarization? Vet Immunol Immunopathol. 2015 Dec 15;168(3-4):131-4. doi: 10.1016/j.vetimm.2015.10.008. Epub 2015 Nov 4. Review. PubMed PMID: 26672910.

[11] Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. 1986. J Immunol. 2005 Jul 1;175(1):5-14. PubMed PMID: 15972624.

[12] Mosmann TR, Sad S. The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol Today. 1996 Mar;17(3):138-46. Review. PubMed PMID: 8820272.

[13]Neurath MF, Finotto S, Glimcher LH. The role of Th1/Th2 polarization in mucosal immunity. Nat Med. 2002 Jun;8(6):567-73. Review. PubMed PMID: 12042806.

[14] Wang H, Zhang D, Han Q, Zhao X, Zeng X, Xu Y, Sun Z, Chen Q. Role of distinct  CD4(+) T helper subset in pathogenesis of oral lichen planus. J Oral Pathol Med.  2016 Jul;45(6):385-93. doi: 10.1111/jop.12405. Epub 2015 Dec 23. Review. PubMed PMID: 26693958.

[15] Zhu J. T helper 2 (Th2) cell differentiation, type 2 innate lymphoid cell (ILC2) development and regulation of interleukin-4 (IL-4) and IL-13 production. Cytokine. 2015 Sep;75(1):14-24. doi: 10.1016/j.cyto.2015.05.010. Epub 2015 Jun 1.Review. PubMed PMID: 26044597; PubMed Central PMCID: PMC4532589.

[16] Compalati E, Braido F, Canonica GW. An update on allergen immunotherapy and asthma. Curr Opin Pulm Med. 2014 Jan;20(1):109-17. doi:10.1097/MCP.0000000000000016. Review. PubMed PMID: 24296688.

[17] Lit LC, Wong CK, Li EK, Tam LS, Lam CW, Lo YM. Elevated gene expression of Th1/Th2 associated transcription factors is correlated with disease activity in patients with systemic lupus erythematosus. J Rheumatol. 2007 Jan;34(1):89-96.Epub 2006 Nov 15. PubMed PMID: 17117487.

[18] Azar ST, Tamim H, Beyhum HN, Habbal MZ, Almawi WY. Type I (insulin-dependent) diabetes is a Th1- and Th2-mediated autoimmune disease. Clin Diagn Lab Immunol. 1999 May;6(3):306-10. Review. PubMed PMID: 10225827; PubMed Central PMCID: PMC103714

[19] Zimmermann M. Ethical guidelines for investigations of experimental pain in conscious animals. Pain. 1983 Jun;16(2):109-10. PubMed PMID: 6877845.

[20] Kobayashi H, Kikuchi S, Konno S, Kato K, Sekiguchi M. Interaction of 5-hydroxytryptamine and tumor necrosis factor-α to pain-related behavior by nucleus pulposus applied on the nerve root in rats. Spine (Phila Pa 1976). 2011 Feb 1;36(3):210-8. doi: 10.1097/BRS.0b013e3181fea618. PubMed PMID: 21248590.

[21] Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksh TL. Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods. 1994 Jul;53(1):55-63. PubMed PMID: 7990513.

[22] Zhu X, Cao S, Zhu MD, Liu JQ, Chen JJ, Gao YJ. Contribution of chemokine CCL2/CCR2 signaling in the dorsal root ganglion and spinal cord to the maintenance of neuropathic pain in a rat model of lumbar disc herniation. J Pain. 2014 May;15(5):516-26. doi: 10.1016/j.jpain.2014.01.492. Epub 2014 Jan 23. PubMed PMID: 24462503.

[23] Biswas SK, Mantovani A. Macrophage plasticity and interaction with lymphocyte  subsets: cancer as a paradigm. Nat Immunol. 2010 Oct;11(10):889-96. doi: 10.1038/ni.1937. Epub 2010 Sep 20. Review. PubMed PMID: 20856220.

[24] de Souza Grava AL, Ferrari LF, Defino HL. Cytokine inhibition and time-related influence of inflammatory stimuli on the hyperalgesia induced by the nucleus pulposus. Eur Spine J. 2012 Mar;21(3):537-45. doi: 10.1007/s00586-011-2027-8. Epub 2011 Sep 25. PubMed PMID: 21947908; PubMed Central PMCID: PMC3296850.

[25]Heilmann RM, Suchodolski JS. Is inflammatory bowel disease in dogs and cats associated with a Th1 or Th2 polarization? Vet Immunol Immunopathol. 2015 Dec 15;168(3-4):131-4. doi: 10.1016/j.vetimm.2015.10.008. Epub 2015 Nov 4. Review. PubMed PMID: 26672910.

[26]Molinos M, Almeida CR, Caldeira J, Cunha C, Gonçalves RM, Barbosa MA. Inflammation in intervertebral disc degeneration and regeneration. J R Soc Interface. 2015 Mar 6;12(104):20141191. doi: 10.1098/rsif.2014.1191. Review. Erratum in: J R Soc Interface. 2015 Jul 6;12(108):20150429. PubMed PMID: 25673296; PubMed Central PMCID: PMC4345483.

[27]You C, Zhu K, Liu X, Xi C, Zhang Z, Xu G, Yan J. Tumor necrosis factor-α-dependent infiltration of macrophages into the dorsal root ganglion in a rat disc herniation model. Spine (Phila Pa 1976). 2013 Nov 1;38(23):2003-7. doi: 10.1097/BRS.0b013e3182a84701. PubMed PMID: 23963020.

[28]Ricardo SD, van Goor H, Eddy AA. Macrophage diversity in renal injury and repair. J Clin Invest. 2008 Nov;118(11):3522-30. doi: 10.1172/JCI36150. Review. PubMed PMID: 18982158; PubMed Central PMCID: PMC2575702.

[29]Gordon S, Martinez FO. Alternative activation of macrophages: mechanism and functions. Immunity. 2010 May 28;32(5):593-604. doi: 10.1016/j.immuni.2010.05.007. Review. PubMed PMID: 20510870.

[30] Coffman RL, Seymour BW, Hudak S, Jackson J, Rennick D. Antibody to interleukin-5 inhibits helminth-induced eosinophilia in mice. Science. 1989 Jul 21;245(4915):308-10. PubMed PMID: 2787531.

[31] Calvo M, Dawes JM, Bennett DL. The role of the immune system in the generation of neuropathic pain. Lancet Neurol. 2012 Jul;11(7):629-42. doi: 10.1016/S1474-4422(12)70134-5. Review. PubMed PMID: 22710756.

[32] Liou JT, Yuan HB, Mao CC, Lai YS, Day YJ. Absence of C-C motif chemokine ligand 5 in mice leads to decreased local macrophage recruitment and behavioral hypersensitivity in a murine neuropathic pain model. Pain 2012;153(6):1283-1291


Refbacks

  • There are currently no refbacks.


Creative Commons Attribution-NonCommercial 3.0

This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.