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. 2017 Dec;6(12):656-664.
doi: 10.1302/2046-3758.612.BJR-2017-0112.R1.

Cytokines in tendon disease: A Systematic Review

W Morita  1 , S G Dakin  1 , S J B Snelling  1 , A J Carr  2
Affiliations

Cytokines in tendon disease: A Systematic Review

W Morita et al. Bone Joint Res. 2017 Dec.

Abstract

Objectives: Emerging evidence indicates that tendon disease is an active process with inflammation that is critical to disease onset and progression. However, the key cytokines responsible for driving and sustaining inflammation have not been identified.

Methods: We performed a systematic review of the literature using MEDLINE (U.S. National Library of Medicine, Bethesda, Maryland) in March 2017. Studies reporting the expression of interleukins (ILs), tumour necrosis factor alpha (TNF-α) and interferon gamma in diseased human tendon tissues, and animal models of tendon injury or exercise in comparison with healthy control tissues were included.

Results: IL-1β, IL-6, IL-10, and TNF-α are the cytokines that have been most frequently investigated. In clinical samples of tendinopathy and tendon tears, the expression of TNF-α tended not to change but IL-6 increased in tears. Healthy human tendons showed increased IL-6 expression after exercise; however, IL-10 remained unchanged. Animal tendon injury models showed that IL-1β, IL-6, and TNF-α tend to increase from the early phase of tendon healing. In animal exercise studies, IL-1β expression showed a tendency to increase at the early stage after exercise, but IL-10 expression remained unchanged with exercise.

Conclusions: This review highlights the roles of IL-1β, IL-6, IL-10, and TNF-α in the development of tendon disease, during tendon healing, and in response to exercise. However, there is evidence accumulating that suggests that other cytokines are also contributing to tendon inflammatory processes. Further work with hypothesis-free methods is warranted in order to identify the key cytokines, with subsequent mechanistic and interaction studies to elucidate their roles in tendon disease development.Cite this article: W. Morita, S. G. Dakin, S. J. B. Snelling, A. J. Carr. Cytokines in tendon disease: A Systematic Review. Bone Joint Res 2017;6:656-664. DOI: 10.1302/2046-3758.612.BJR-2017-0112.R1.

Keywords: Cytokine; Tendinopathy; Tendon.

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Conflict of interest statement

Conflict of Interest Statement: None declared

Figures

Fig. 1
Fig. 1
Flowchart of the systematic review protocol.
Fig. 2
Fig. 2
Number of studies of human tendon tissues and animal tendon injury or exercise models for each cytokine.
See this image and copyright information in PMC

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References

    1. Forde MS, Punnett L, Wegman DH. Prevalence of musculoskeletal disorders in union ironworkers. J Occup Environ Hyg 2005;2:203-212. - PubMed
    1. Dean BJ, Franklin SL, Carr AJ. A systematic review of the histological and molecular changes in rotator cuff disease. Bone Joint Res 2012;1:158-166. - PMC - PubMed
    1. Schulze-Tanzil G, Al-Sadi O, Wiegand E, et al. The role of pro-inflammatory and immunoregulatory cytokines in tendon healing and rupture: new insights. Scand J Med Sci Sports 2011;21:337-351. - PubMed
    1. Neer CS, Welsh RP. Shoulder in Sports. Orthop Clin North Am 1977;8:583-591. - PubMed
    1. Wang JH, Iosifidis MI, Fu FH. Biomechanical basis for tendinopathy. Clin Orthop Relat Res 2006;443:320-332. - PubMed