Interleukin-27 is associated with the pathogenesis of lumbar disc herniation

doi:10.12307/2022.678

Abstract

Abstract: BACKGROUND: Inflammation is an important mechanism underlying lumbar disc herniation. Th17 cells play a key role in immune activation. Interleukin-27 can inhibit Th17 cell differentiation by down-regulating the expression of interleukin-6 and transforming growth factor-β, and plays an important role in a variety of autoimmune diseases. However, little is known about the relationship between interleukin-27 and lumbar disc herniation.
OBJECTIVE: To investigate the levels of interleukin-27 in patients with lumbar disc herniation, and to explore their association with lumbar intervertebral disc herniation.
METHODS: This study enrolled 36 patients with lumbar disc herniation, 18 healthy controls, and 8 patients undergoing emergency surgery for thoracolumbar burst fracture. Patients with lumbar disc herniation received posterior fenestration discectomy, posterior lumbar interbody fusion (PLIF) or transforaminal lumbar interbody fusion. The pain intensity of the patients was scored using a visual analogue scale (VAS) before operation. Serum interleukin-27 and interleukin-17 levels in peripheral blood were determined by enzyme linked immunosorbent assay (ELISA). Samples of nucleus pulposus from patients with lumbar disc herniation and those with thoracolumbar burst fractures (considered as normal nucleus pulposus samples) were taken for detection of interleukin-27 and interleukin-17 mRNA and protein using quantitative real-time PCR and western blot assay, respectively.
RESULTS AND CONCLUSION: Patients with lumbar disc herniation had significantly higher serum interleukin-27 levels than healthy controls (P < 0.001). Interleukin-17 levels were also significantly higher in the patients with lumbar disc herniation. The protein and mRNA expression levels of interleukin-27 and interleukin-17 in the nucleus pulposus were significantly higher in patients with lumbar disc herniation than patients with thoracolumbar burst fractures (P < 0.001). The expression of interleukin-27 was significantly higher in patients with mild pain than those with severe pain (P < 0.01). To conclude, inflammation is responsible for the pain experienced by patients with lumbar disc herniation, and interleukin-27 is involved in the pathogenesis of lumbar disc herniation.

Key words: interleukin-27, interleukin-17, lumbar disc herniation, blood, nucleus pulposus, intervertebral disc

CLC Number:

Xue Huawei, Zhu Min, Li Yuqian. Interleukin-27 is associated with the pathogenesis of lumbar disc herniation[J]. Chinese Journal of Tissue Engineering Research, 2022, 26(23): 3750-3755.

Figures/Tables 4

References

[1] GILBERTSON L, AHN SH, TENG PN, et al. The effects of recombinant human bone morphogenetic protein-2, recombinant human bone morphogenetic protein-12, and adenoviral bone morphogenetic protein-12 on matrix synthesis in human annulus fibrosis and nucleus pulposus cells. Spine J. 2008;8(3):449-456.
[2] SCHWARZER AC, APRILL CN, DERBY R, et al. The prevalence and clinical features of internal disc disruption in patients with chronic low back pain. Spine (Phila Pa 1976). 1995;20(17):1878-1883.
[3] 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;21(3):537-545.
[4] KIM HJ, YEOM JS, KOH YG, et al. Anti-inflammatory effect of platelet-rich plasma on nucleus pulposus cells with response of TNF-α and IL-1. J Orthop Res. 2014;32(4):551-556.
[5] WEILER C, NERLICH AG, BACHMEIER BE, et al. Expression and distribution of tumor necrosis factor alpha in human lumbar intervertebral discs: a study in surgical specimen and autopsy controls. Spine (Phila Pa 1976). 2005;30(1):44-53; discussion 54.
[6] KEPLER CK, MARKOVA DZ, DIBRA F, et al. Expresion and relationship of proinflammatory chemokine RANTES/CCL5 and cytokine IL-1β in painful human intervertebral discs. Spine (Phila Pa 1976). 2013;38(11):873-880.
[7] SAAL JS, FRANSON RC, DOBROW R, et al. High levels of inflammatory phospholipase A2 activity in lumbar disc herniations. Spine (Phila Pa 1976). 1990;15(7):674-678.
[8] O’DONNELL JL, O’DONNELL AL. Prostaglandin E2 content in herniated lumbar disc disease. Spine (Phila Pa 1976). 1996;21(14):1653-1655; discussion 1655-1656.
[9] KARPPINEN J, DAAVITTILA I, NOPONEN N, et al. Is the interleukin-6 haplotype a prognostic factor for sciatica? Eur J Pain. 2008;12(8):1018-1025.
[10] CHENG L, FAN W, LIU B, et al. Th17 lymphocyte levels are higher in patients with ruptured than non-ruptured lumbar discs, and are correlated with pain intensity. Injury. 2013;44(12):1805-1810.
[11] XUE H, YAO Y, WANG X, et al. Interleukin-21 Is Associated with the Pathogenesis of Lumbar Disc Herniation. Iran J Allergy Asthma Immunol. 2015;14(5):509-518.
[12] JIANG H, DENG Y, WANG T, et al. Interleukin-23 may contribute to the pathogenesis of lumbar disc herniation through the IL-23/IL-17 pathway. J Orthop Surg Res. 2016;11:12.
[13] PFLANZ S, TIMANS JC, CHEUNG J, et al. IL-27, a heterodimeric cytokine composed of EBI3 and p28 protein, induces proliferation of naive CD4+ T cells. Immunity. 2002;16:779-790.
[14] MEKA RR, VENKATESHA SH, DUDICS S, et al. IL-27-induced modulation of autoimmunity and its therapeutic potential. Autoimmun Rev. 2015; 14(12):1131-1141.
[15] HUBER M, STEINWALD V, GURALNIK A, et al. IL-27 inhibits the development of regulatory T cells via STAT3. Int Immunol. 2008;20: 223-234.
[16] LUCAS S, GHILARDI N, LI J, et al. IL-27 regulates IL-12 responsiveness of naive CD4+ T cells through Stat1-dependent and -independent mechanisms. Proc Natl Acad Sci U S A. 2003;100:15047-15052.
[17] FUJIMOTO H, HIRASE T, MIYAZAKI Y, et al. IL-27 inhibits hyperglycemia and pancreatic islet inflammation induced by streptozotocin in mice. Am J Pathol. 2011;179:2327-2336.
[18] TANIDA S, YOSHITOMI H, ISHIKAWA M, et al. IL-27-producing CD14(+) cells infiltrate inflamed joints of rheumatoid arthritis and regulate inflammation and chemotactic migration. Cytokine. 2011;55:237-244.
[19] TANG SC, FAN XH, PAN QM, et al. Decreased expression of IL-27 and its correlation with Th1 and Th17 cells in progressive multiple sclerosis. J Neurol Sci. 2015;348:174-180.
[20] SASAOKA T, ITO M, YAMASHITA J, et al. Treatment with IL-27 attenuates experimental colitis through the suppression of the development of IL-17-producing T helper cells. Am J Physiol Gastrointest Liver Physiol. 2011;300:G568-576.
[21] XIA LP, LI BF, SHEN H, et al. Interleukin-27 and interleukin-23 in patients with systemic lupus erythematosus: possible role in lupus nephritis. Scand J Rheumatol. 2015;44:200-205.
[22] TOJO G, FUJIMURA T, KAMBAYASHI Y, et al. Systemic Lupus Erythematosus Accompanied by Psoriasis Induces IL-27-Producing Cells in Both Affected Areas of the Skin. Case Rep Dermatol . 2012;4(2):181-185.
[23] MACNAB I. Cervical spondylosis. Clin Orthop Relat Res. 1975;(109):69-77.
[24] DI MARTINO A, MERLINI L, FALDINI C. Autoimmunity in intervertebral disc herniation: from bench to bedside. Expert Opin Ther Targets. 2013; 17(12):1461-1470.
[25] SATOH K, KONNO S, NISHIYAMA K, et al. Presence and distribution of antigen-antibody complexes in the herniated nucleus pulposus. Spine (Phila Pa 1976). 1999;24(19):1980-1984.
[26] ARAI Y, YASUMA T, SHITOTO K, et al. Immunohistological study of intervertebral disc herniation of lumbar spine. J Orthop Sci. 2000;5(3): 229-231.
[27] GEISS A, LARSSON K, RYDEVIK B, et al. Autoimmune properties of nucleus pulposus: an experimental study in pigs. Spine (Phila Pa 1976). 2007;32(2):168-173.
[28] MURAI K, SAKAI D, NAKAMURA Y, et al. Primary immune system responders to nucleus pulposus cells: evidence for immune response in disc herniation. Eur Cell Mater. 2010;19:13-21.
[29] NAYLOR A, HAPPEY F, TURNER RL, et al. Enzymic and immunological activity in the intervertebral disk. Orthop Clin North Am. 1975;6(1):51-58.
[30] JAFARZADEH A, NEMATI M, CHAUHAN P, et al. Interleukin-27 Functional Duality Balances Leishmania Infectivity and Pathogenesis. Front Immunol. 2020;11:1573.
[31] JONES GW, HILL DG, CARDUS A, et al. IL-27: a double agent in the IL-6 family. Clin Exp Immunol. 2018;193(1):37-46.
[32] YOSHIDA H, HUNTER CA. The immunobiology of interleukin-27. Ann Rev Immunol. 2015;33:417-443.
[33] HALL A, SILVER J, HUNTER C. The immunobiology of IL-27. AdvImmunol. 2012;115:1-44.
[34] HUNTER CA, KASTELEIN R. Interleukin-27: balancing protective and pathological immunity. Immunity. 2012;37:960-969.
[35] KORN T, OUKKA M, KUCHROO V, et al. Th17 cells: effector T cells with inflammatory properties. Semin Immunol. 2007;19(6):362-371.
[36] SASAGURI T, TAGUCHI T, MURATA Y, et al. Interleukin-27 controls basal pain threshold in physiological and pathological conditions. Sci Rep. 2018;8:11022.
[37] OWAKI T, ASAKAWA M, KAMIYA S, et al. IL-27 suppresses CD28-mediated [correction of medicated] IL-2 production through suppressor of cytokine signaling 3. J Immunol. 2006;176:2773-2780.
[38] 冯勇军,王明婧,曾春蓉,等. 变应性鼻炎患者血清Th细胞亚群及相关细胞因子水平变化[J].山东医药,2016,56(9):69-70.
[39] 陈毅斐,高亚东,胡家豪,等. 白细胞介素27在自身免疫性疾病中的功能调控[J]. 医学综述,2017,23(22):4376-4381.
[40] 李阳,夏丽坤. 白细胞介素-27的生物学功能及其抗病毒作用的研究进展[J].国际免疫学杂志,2015,38(2):195-198.
[41] 单敏敏,李长安,崔红生. 哮喘宁颗粒对哮喘大鼠Th1/Th2平衡和STAT1通路调节作用的研究[J]. 中国医药导报,2019,16(10):11-15.
[42] 任媛媛,王贵强. 白细胞介素27在抗病毒免疫中的作用及临床应用前景[J]. 国际流行病学传染病学杂志,2011,38(6):425-428.
[43] 冯硕,崔德成. 自拟通窍止咳汤治疗儿童上气道咳嗽综合征疗效观察[J]. 现代中西医结合杂志,2020,29(11):1215-1218.
[44] 杨景英,陈学利,吴文钦,等. 白细胞介素-12家族与感染性疾病相关研究进展[J]. 临床检验杂志,2014,32(6):443-446.