A systematic review of inflammatory cells and markers in human tendinopathy

Abstract

Background: This article systematically reviews the current evidence regarding inflammation in Tendinopathy with the aim to increase understanding of a potential common pathophysiology. Methods: Following the PRISMA statements, the terms: (tendinopathy OR (tendons AND rupture)) AND (inflammation OR (inflammation AND cells) OR immune system OR inflammation mediators OR bacteria) were used. One thousand four hundred thirty-one articles were identified which was screened down to 53. Results: 39/53 studies mentioned inflammatory cells but had contradicting conclusions. Macrophages were the most common cell type and inflammatory markers were detectable in all the articles which measure them. Conclusions: The included studies show different conclusions, but this heterogeneity is not unexpected since the clinical criteria of 'tendinopathy' encompass a huge clinical spectrum. Different 'tendinopathy' conditions may have different pathophysiology, and even the same clinical condition may be at different disease stages during sampling, which can alter the histological and biochemical picture. Control specimen sampling was suboptimal since the healthy areas of the pathological-tendon may actually be subclinically diseased, as could the contralateral tendon in the same subject. Detection of inflammatory cells is most sensitive using immunohistochemistry targeting the cluster of differentiation markers, especially when compared to the conventional haematoxylin and eosin staining methods. The identified inflammatory cell types favour a chronic inflammatory process; which suggests a persistent stimulus. This means NSAID and glucocorticoids may be useful since they suppress inflammation, but it is noted that they may hinder tendon healing and cause long term problems. This systematic review demonstrates a diversity of data and conclusions in regard to inflammation as part of the pathogenesis of Tendinopathy, ranging from ongoing or chronic inflammation to non-inflammatory degeneration and chronic infection. Whilst various inflammatory markers are present in two thirds of the reviewed articles, the heterogenicity of data and lack of comparable studies means we cannot conclude a common pathophysiology from this systematic review.

Local Shifts in Inflammatory and Resolving Lipid Mediators in Response to Tendon Overuse

“…However, an apparent lack of polymorphonuclear leukocytes (PMNs) within diseased tendons led to the view that tendinopathy is rather a degenerative condition of tendinosis that is devoid of inflammation (20). Nevertheless, recent studies employing modern antibody based immunohistochemical staining techniques demonstrate that leukocytes, most notably macrophages (MΦ), are indeed often present within diseased human tendons (21), stimulating a resurgence of interest into the potential role of inflammation in tendon biology (22).…”

Bringing tendon biology to heel: Leveraging mechanisms of tendon development, healing, and regeneration to advance therapeutic strategies

“…Schubert et al 166 provided one of the first pieces of experimental evidence demonstrating the infiltration of myeloid cells and lymphocytes in Achilles tendinopathy patients. Many studies have since corroborated and extended these findings in human patellar, Achilles, and rotator cuff tendinopathies 6,160,167‐176 and animal models 129,159,177‐180 . Comparison of Achilles tendinopathic tissue with spontaneously ruptured Achilles tendons revealed higher levels of granulocytes in ruptured tendons, while macrophages, mast cells, and lymphocytes were more prevalent in diseased tendons, suggesting immune‐related events differ between tendinopathy vs spontaneous acute injury 166 …”

Macrophage depletion impairs neonatal tendon regeneration

“…[12][13][14][15] However, the role of these macrophage populations in promoting or inhibiting tendon healing remains unclear. 16 While therapeutic strategies that enhance the presence of M2-like macrophages appear to promote functional tendon healing, 17,18 other studies suggest that increased M2-like macrophage polarization can also drive fibrotic scar formation. 19 Most of these studies are correlative however, and there are still very few studies that directly test the role of macrophages in tendon healing via ablation or depletion.…”