Expression of interleukin-18 in muscle tissue of patients with polymyositis or dermatomyositis and effects of conventional immunosuppressive treatment

Helmers, Sevim Barbasso; Bruton, Mei; Loell, Ingela; Ulfgren, Ann‐Kristin; Gracie, Alastair; McInnes, Iain B.; Lundberg, Ingrid E.

doi:10.1093/rheumatology/key222

Cited by 14 publications

(11 citation statements)

References 41 publications

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“…51 IL-18 may be also involved in regulating intramuscular lipid metabolism and hypertriglyceridemia, controlling local access to energy stores. 52,53 While high intramuscular expression of IL-18 has been reported in inflammatory diseases and myopathies, 54,55 the IL-18 concentrations did not appear to follow the trends in the Oil Red O staining (Figure 8). Taken together, perhaps the effects and interactions of IL-1β, IL-18, and IFNγ prolonged upregulation of satellite cell proliferation combined with regulation of injury lipogenesis and inflammation contributed to the increased contraction force.…”

Section: Discussionmentioning

confidence: 89%

Intramuscular injection of skeletal muscle derived extracellular matrix mitigates denervation atrophy after sciatic nerve transection

et al. 2021

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Peripheral nerve injury and the associated muscle atrophy has an estimated annual healthcare burden of $150 billion dollars in the United States. When considering the total annual health-related spending of $3.5 trillion, these pathologies alone occupy about 4.3%. The prevalence of these ailments is rooted, at least in part, in the lack of specific preventative therapies that can be administered to muscle while it remains in the denervated state. To address this, skeletal muscle-derived ECM (skECM) was injected directly in denervated muscle with postoperative analysis performed at 20 weeks, including gait analysis, force production, cytokine quantification, and histological analysis. skECM was shown to be superior against non-injected muscle controls showing no difference in contraction force to uninjured muscle at 20 weeks. Cytokines IL-1β, IL-18, and IFNγ appeared to mediate regeneration with statistical regression implicating these cytokines as strong predictors of muscle contraction, showing significant linear correlation.

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Section: Discussionmentioning

confidence: 89%

Intramuscular injection of skeletal muscle derived extracellular matrix mitigates denervation atrophy after sciatic nerve transection

et al. 2021

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“…Under the action of IL18, these two subunits show a high affinity and form a complex, thus activating intracellular signaling pathways, such as NF-κB and AP-1 transcription factors ( Yasuda et al, 2019 ). Previous studies have shown that an increased serum IL18 correlated with ILD in DM ( Gono et al, 2010 ), and that IL18 was expressed in muscle infiltrating cells of patients with myositis ( Helmers et al, 2018 ). Moreover, endothelial cells, smooth muscle cells and CD8 + cells expressed a high content of IL18R ( Tucci et al, 2006 ).…”

Section: Discussionmentioning

confidence: 99%

The Expression of Cytokine Profiles and Related Receptors in Idiopathic Inflammatory Myopathies

Zhou

Zhao

et al. 2022

Front. Pharmacol.

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Background: Cytokines play a vital role in the pathogenesis of idiopathic inflammatory myopathies (IIMs). Here, we investigated the expression of serum cytokine profiles in untreated IIMs and their correlations with clinical indicators, and further studied the expression of related cytokines receptors in IIMs.Methods: The Human 48-Plex Luminex assay for cytokines was performed in the serum of IIMs, including 93 untreated and 18 follow-up (39 samples) patients, and 32 healthy controls (HC). Mann-Whitney U test with bonferroni adjusted was used to identify the differentially expressed cytokines among groups. Celltalker software was used to identify the receptors of differentially expressed cytokines. The expression of receptors was further validated by published GEO datasets (muscle, blood and skin), RT-qPCR, western blot and flow cytometry.Results: The serum levels of Eotaxin, IL7, IL18, IP10, MCP1, MCSF, MIG and SCGFβ were elevated in the 93 untreated patients. Except for IL7, all other cytokines were decreased after treatment and their levels were positively correlated with clinical indices such as LDH, ESR, CRP, ALT, IgA, AST and IgG while negatively correlated with albumin and MMT8. According to the serum myositis-specific antibodies (MSAs), patients were classified into three groups: anti-ARS (Jo-1, OJ, EJ, PL7, PL12), anti-MDA5 positive, and anti-TIF1γ positive. Compared with HC, the levels of IP10 and MIG were increased in three groups. Moreover, IL18 and MSCF were increased in anti-ARS patients, and CTACK, Eotaxin, IL1Rα, IL7, IL18, MCP1, MCP3, MCSF and SCGFβ were elevated in anti-MDA5 patients. Twenty receptors of the 8 differentially expressed cytokines were matched by celltalker software, among them, IL18R1 and CCR1 were up-regulated in blood, muscle and skin of IIMs from the analysis of GEO published datasets. RT-qPCR and western blot further validated IL18R1 was upregulated in the muscle tissues of dermatomyositis. The number of IL18R1+CD4+ cells was increased while IL18R1+CD8+ cells was decreased in peripheral blood of anti-MDA5 patients.Conclusion: This study showed that cytokine profiles were significantly changed in IIMs, and different MSA groups had unique cytokine expression patterns. The levels of some cytokine were correlated with clinical indices. The IL18 receptor IL18R1 might play important roles in IIMs.

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“…IL-18 has previously been identified to be elevated in DM muscle biopsies, and expression decreases with immunosuppressive treatment for the muscle disease ( 22 ). In the skin, activation of IL-18 has been identified as important in other autoimmune and inflammatory skin diseases such as vitiligo, atopic dermatitis, and alopecia areata ( 23 ).…”

Section: Discussionmentioning

confidence: 99%

IL18-containing 5-gene signature distinguishes histologically identical dermatomyositis and lupus erythematosus skin lesions

Tsoi¹,

Gharaee−Kermani²,

Berthier³

et al. 2020

JCI Insight

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Skin lesions in dermatomyositis (DM) are common, are frequently refractory, and have prognostic significance. Histologically, DM lesions appear similar to cutaneous lupus erythematosus (CLE) lesions and frequently cannot be differentiated. We thus compared the transcriptional profile of DM biopsies with CLE lesions to identify unique features. Type I IFN signaling, including IFN-κ upregulation, was a common pathway in both DM and CLE; however, CLE also exhibited other inflammatory pathways. Notably, DM lesions could be distinguished from CLE by a 5-gene biomarker panel that included IL18 upregulation. Using single-cell RNA-sequencing, we further identified keratinocytes as the main source of increased IL-18 in DM skin. This study identifies a potentially novel molecular signature, with significant clinical implications for differentiating DM from CLE lesions, and highlights the potential role for IL-18 in the pathophysiology of DM skin disease.

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Expression of interleukin-18 in muscle tissue of patients with polymyositis or dermatomyositis and effects of conventional immunosuppressive treatment

Abstract: IL-18 is highly expressed in muscle tissue in the context of inflammatory myopathies and based on its plausible effector functions could provide a novel therapeutic target in future.

Cited by 14 publications

References 41 publications

Intramuscular injection of skeletal muscle derived extracellular matrix mitigates denervation atrophy after sciatic nerve transection

Intramuscular injection of skeletal muscle derived extracellular matrix mitigates denervation atrophy after sciatic nerve transection

The Expression of Cytokine Profiles and Related Receptors in Idiopathic Inflammatory Myopathies

IL18-containing 5-gene signature distinguishes histologically identical dermatomyositis and lupus erythematosus skin lesions

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