Vol 69, No 3 (2018)
Original paper
Published online: 2018-05-09
Th17 and IL-17 exhibit higher levels in osteonecrosis of the femoral head and have a positive correlation with severity of pain
Abstract
Objective: Synovitis associated with osteonecrosis of the femoral head (ONFH) is responsible for several clinical symptoms. However, the mechanisms underlying synovitis and the inflammatory environment remain unclear. This study analyzed the proinflammatory mediation expression of IL-17 and Th17, which perform key functions in regulating inflammatory processes in the inflamed synovium and peripheral blood in ONFH.
Methods: Synovial fluid from the hips of 23 patients and 5 controls was collected during surgery, and peripheral blood samples were obtained from 34 patients and 9 controls. The expression of IL-17 in the synovium was detected by immunohistochemistry, and the levels of Th17 and IL-17 in the blood were measured by flow cytometry and ELISA. Pain assessment was performed for all the patients and controls.
Results: An inflamed synovium was characterized by increased leukocyte infiltration and IL-17 expression in comparison with the control. Preoperative levels of Th17 and IL-17 were significantly higher in the peripheral blood of the ONFH group than those in the controls. The symptoms were also positively correlated with the Th17 levels of the ONFH patients.
Conclusion: Th17 cells were recruited to an inflamed synovium, and inflammatory cytokine IL-17 was expressed at an increased level in the hip synovium of ONFH patients, which possibly contributed to clinical syndrome development. Overall, this study will help in identifying new therapeutic strategies for ONFH, especially the targeting of IL-17 to decrease inflammation and pain. < p > < /p >
Keywords: T helper 17 lymphocyteIL-17osteonecrosis of femoral headinflammationpainvisual analogue scale
References
- MONT M, MARULANDA G, JONES L, et al. Systematic analysis of classification systems for osteonecrosis of the femoral head. J Bone Joint Surg Am. 2006; 88: 16–26.
- Seamon J, Keller T, Saleh J, et al. The pathogenesis of nontraumatic osteonecrosis. Arthritis. 2012; 2012: 601763.
- Malizos K, Karantanas A, Varitimidis S, et al. Osteonecrosis of the femoral head: Etiology, imaging and treatment. Eur J Radiol. 2007; 63(1): 16–28.
- Jingushi S, Lohmander L, Shinmei M, et al. Markers of joint tissue turnover in joint fluids from hips with osteonecrosis of the femoral head. J Orthop Res. 2000; 18(5): 728–733.
- Kamiya N, Yamaguchi R, Adapala N, et al. Legg-Calvé-Perthes Disease Produces Chronic Hip Synovitis and Elevation of Interleukin-6 in the Synovial Fluid. J Bone Miner Res. 2015; 30(6): 1009–1013.
- Yamaguchi R, Kamiya N, Adapala N, et al. HIF-1-Dependent IL-6 Activation in Articular Chondrocytes Initiating Synovitis in Femoral Head Ischemic Osteonecrosis. J Bone Joint Surg Am. 2016; 98(13): 1122–1131.
- Zhao D, Xiaobing Y, Wang T, et al. Digital subtraction angiography in selection of the vascularized greater trochanter bone grafting for treatment of osteonecrosis of femoral head. Microsurgery. 2013; 33(8): 656–659.
- Rabquer BJ, Tan GJ, Shaheen PJ, et al. Synovial inflammation in patients with osteonecrosis of the femoral head. Clin Transl Sci. 2009; 2(4): 273–278.
- Shirai C, Ohtori S, Kishida S, et al. The pattern of distribution of PGP 9.5 and TNF-alpha immunoreactive sensory nerve fibers in the labrum and synovium of the human hip joint. Neurosci Lett. 2009; 450(1): 18–22.
- Wang CJ, Yang YJ, Huang CC. The effects of shockwave on systemic concentrations of nitric oxide level, angiogenesis and osteogenesis factors in hip necrosis. Rheumatol Int. 2011; 31(7): 871–877.
- Saidi S, Magne D. Interleukin-33: a novel player in osteonecrosis of the femoral head? Joint Bone Spine. 2011; 78(6): 550–554.
- Lim JC, Mitchell CH. Inflammation, pain, and pressure--purinergic signaling in oral tissues. J Dent Res. 2012; 91(12): 1103–1109.
- Stemkowski PL, Smith PA. Sensory neurons, ion channels, inflammation and the onset of neuropathic pain. Can J Neurol Sci. 2012; 39(4): 416–435.
- Ji RR, Xu ZZ, Strichartz G, et al. Emerging roles of resolvins in the resolution of inflammation and pain. Trends in Neurosciences. 2011; 34(11): 599–609.
- Deligne C, Casulli S, Pigenet A, et al. Differential expression of interleukin-17 and interleukin-22 in inflamed and non-inflamed synovium from osteoarthritis patients. Osteoarthritis and Cartilage. 2015; 23(11): 1843–1852.
- Wei M. Correlation of IL-17 level in synovia and severity of knee osteoarthritis. Med Sci Monit. 2015; 21: 1732–1736.
- Wilke C, Bishop K, Fox D, et al. Deciphering the role of Th17 cells in human disease. Trends Immunol. 2011; 32(12): 603–611.
- Annunziato F, Cosmi L, Santarlasci V, et al. Phenotypic and functional features of human Th17 cells. J Exp Med. 2007; 204(8): 1849–1861.
- Cosmi L, De Palma R, Santarlasci V, et al. Human interleukin 17-producing cells originate from a CD161+CD4+ T cell precursor. J Exp Med. 2008; 205(8): 1903–1916.
- Kleinschek MA, Boniface K, Sadekova S, et al. Circulating and gut-resident human Th17 cells express CD161 and promote intestinal inflammation. J Exp Med. 2009; 206(3): 525–534.
- Kryczek I, Banerjee M, Cheng P, et al. Phenotype, distribution, generation, and functional and clinical relevance of Th17 cells in the human tumor environments. Blood. 2009; 114(6): 1141–1149.
- Miljkovic D, Trajkovic V. Inducible nitric oxide synthase activation by interleukin-17. Cytokine Growth Factor Rev. 2004; 15(1): 21–32.
- H. Xiong, L. Wei, B. Peng, IL-17 stimulates the production of the inflammatory chemokines IL-6 and IL-8 in human dental pulp fibroblasts, Int Endod J. 2015; 48: 505–511.
- Zhang Y, Wang H, Ren J, et al. IL-17A synergizes with IFN-γ to upregulate iNOS and NO production and inhibit chlamydial growth. PLoS One. 2012; 7(6): e39214.
- Shamji MF, Setton LA, Jarvis W, et al. Proinflammatory cytokine expression profile in degenerated and herniated human intervertebral disc tissues. Arthritis Rheum. 2010; 62(7): 1974–1982.
- Mannion AF, Brox JI, Fairbank JC. Comparison of spinal fusion and nonoperative treatment in patients with chronic low back pain: long-term follow-up of three randomized controlled trials. Spine J. 2013; 13(11): 1438–1448.
- Jiang Z, Shukla A, Miller BL, et al. Tumor necrosis factor-alpha and the early vein graft. J Vasc Surg. 2007; 45(1): 169–176.
- Hirata T, Osuga Y, Takamura M, et al. Recruitment of CCR6-Expressing Th17 Cells by CCL 20 Secreted from IL-1β-, TNF-α-, and IL-17A-Stimulated Endometriotic Stromal Cells. Endocrinology. 2010; 151(11): 5468–5476.
- Chan WP, Liu YJ, Huang GS, et al. MRI of joint fluid in femoral head osteonecrosis. Skeletal Radiol. 2002; 31(11): 624–630.
- Montella BJ, Nunley JA, Urbaniak JR. Osteonecrosis of the femoral head associated with pregnancy. A preliminary report. J Bone Joint Surg Am. 1999; 81(6): 790–798.