High levels of IL-6 and IL-8 characterize early-on idiopathic pulmonary fibrosis acute exacerbations

Papiris, Spyros; Tomos, Ioannis; Karakatsani, Anna; Spathis, Aris; Korbila, Ioanna; Analitis, Antonis; Kolilekas, Likurgos; Kagouridis, Konstantinos; Loukides, Stelios; Karakitsos, Petros; Manali, Effrosyni D.

doi:10.1016/j.cyto.2017.08.019

Cited by 131 publications

(98 citation statements)

References 16 publications

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“…Elevated levels of several cytokines and chemokines, namely IL-6, IL-8, IL-17, IL-23, etc., were seen in peripheral blood, muscle or skin of IIM patients, and were consistent with disease activity (37). Meanwhile several studies also observed significant elevation of cytokines and chemokines including IL-6, IL-8 in patients with ILD exacerbation, and the elevation was found to be related to worse outcome (38,39). The partially overlapped pathological mechanism made baseline disease activity a valuable predictor of AE-ILD.…”

Section: Discussionmentioning

confidence: 59%

Acute Exacerbation of Interstitial Lung Disease in Adult Patients With Idiopathic Inflammatory Myopathies: A Retrospective Case-Control Study

Liang

Sun

et al. 2020

Front. Med.

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This study aimed at clarifying the prevalence, risk factors, outcome, and outcome-related factors of acute exacerbation of interstitial lung disease (AE-ILD) in patients with idiopathic inflammatory myopathy (IIM). Methods: Data of IIM patients who were admitted to the First Affiliated Hospital of Zhejiang University (FAHZJU) from September 2007 to September 2019 were retrospectively collected. And the IIM patients with AE-ILD formed the case group. In addition, age and sex matched IIM patients without AE-ILD were randomly selected to constitute the control group. A 1:2 case-control study and intragroup analysis were performed to identify risk factors for development of AE-ILD in IIM patients and unfavorable short-term outcome in AE-ILD patients through comparison, univariate and multivariate logistic regression analysis. Results: AE-ILD occurred in 64 out of 665 IIM patients (9.6%) with a short-term mortality rate of 39.1%. And the 64 IIM patients with AE-ILD formed the case group. Besides, 128 age and sex matched IIM patients without AE-ILD were randomly selected to constitute the control group. The retrospective case-control study revealed that elevated on-admission disease activity (P < 0.001), lower percent-predicted diffusing capacity of the lung for carbon monoxide (DLCO%, P = 0.013) and diagnosis of clinically amyopathic dermatomyositis (CADM, P = 0.007) were risk factors for development of AE-ILD in IIM patients. The following intragroup analysis indicated that elevated on-admission disease activity (P = 0.008) and bacterial infection (P = 0.003) were significantly correlated with the unfavorable short-term outcome of patients complicated with AE-ILD. In addition, combined use of steroid and disease modifying antirheumatic drugs (DMARDs, P = 0.006) was found to significantly reduce the short-term mortality in IIM patients with AE-ILD. Conclusion: AE-ILD is a less frequent but fatal complication in IIM patients with elevated on-admission disease activity, lower DLCO% and diagnosis of CADM working as risk factors, indicating the potential roles of autoimmune abnormality and hypoxia in development of AE-ILD. Elevated on-admission disease activity and bacterial infection could predict unfavorable short-term outcome of IIM patients with AE-ILD. A therapeutic regimen of steroid and DMARDs was found to reduce short-term death in these patients.

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Section: Discussionmentioning

confidence: 59%

Acute Exacerbation of Interstitial Lung Disease in Adult Patients With Idiopathic Inflammatory Myopathies: A Retrospective Case-Control Study

Liang

Sun

et al. 2020

Front. Med.

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“…In this study, we established two models: bleomycin‐induced inflammatory model and pulmonary fibrosis model to evaluate the antifibrotic effects of anlotinib. First, in inflammatory models, we found that anlotinib significantly reduced inflammatory cytokines such as IL‐1β, IL‐4, IL‐6 and TNF‐α, which have been demonstrated that were enhanced levels in the lungs of patients with IPF . In addition, anlotinib not only reduced lipid peroxidation levels, but also enhanced SOD activity and total antioxidant capacity in mouse lung tissue.…”

Section: Discussionmentioning

confidence: 99%

“…First, in inflammatory models, we found that anlotinib significantly reduced inflammatory cytokines such as IL-1b, IL-4, IL-6 and TNF-a, which have been demonstrated that were enhanced levels in the lungs of patients with IPF. [20][21][22] In addition, anlotinib not only reduced lipid peroxidation levels, but also enhanced SOD activity and total antioxidant capacity in mouse lung tissue. It is suggested that anlotinib may inhibit early lung injury through suppressing inflammatory response and oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Anlotinib attenuated bleomycin-induced pulmonary fibrosis via the TGF-β1 signalling pathway

Ruan

Liu

et al. 2019

Journal of Pharmacy and Pharmacology

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Objectives Anlotinib hydrochloride (AL3818) is a novel multitarget tyrosine kinase inhibitor which has the same targets as nintedanib, an effective drug has been approved for the treatment of idiopathic pulmonary fibrosis. Here, we examined whether anlotinib could also attenuate bleomycin‐induced pulmonary fibrosis in mice and explored the antifibrosis mechanism. Methods We have evaluated the effect of anlotinib on bleomycin‐induced pulmonary fibrosis in mice. Inflammatory cytokines in alveolar lavage fluid including IL‐1β, IL‐4, IL‐6 and TNF‐α were determined by ELISA. Biomarkers of oxidative stress were measured by corresponding kit. Histopathologic examination was analysed by H&E staining and immunohistochemistry. In vitro, we investigated whether anlotinib inhibited TGFβ/Smad3 and non‐Smad pathways by luciferase assay or Western blotting. We also evaluated whether anlotinib inhibited TGF‐β1‐induced epithelial–mesenchymal transition (EMT) and promoted myofibroblast apoptosis in order to explore the possible molecular mechanism. Key findings The results indicated that anlotinib treatment remarkably attenuated inflammation, oxidative stress and pulmonary fibrosis in mouse lungs. Anlotinib could inhibit the TGF‐β1 signalling pathway. Additionally, anlotinib not only profoundly inhibited TGF‐β1‐induced EMT in alveolar epithelial cells, but also simultaneously reduced the proliferation and promoted the apoptosis in fibroblasts. Conclusions In summary, the results suggest that anlotinib‐mediated suppression of pulmonary fibrosis is related to the inhibition of TGF‐β1 signalling pathway.

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“…[34] IL-8 is a key mediator of IPF-related processes such as cell fibrogenicity; [35] as little as 1 pg/ml increase in serum IL-8 correlates with increased risk of death by 6.7%. [36] Furthermore, IL-8 is a potential IPF biomarker; its levels are increased in the bronchoalveolar fluid, serum and sputum samples of IPF patients. [37] The current study shows that calcilytic treatment significantly reduces IL-8 secretion, suggesting that IL-8 measurements could be used to assess calcilytic efficacy in the clinic.…”

Section: Ipf Diagnosis Is Hampered By the Absence Of Non-invasive Dismentioning

confidence: 99%

Calcium-sensing receptor antagonism as a novel therapeutic for pulmonary fibrosis

Wolffs

Mansfield

Bruce

et al. 2020

Preprint

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Background: Idiopathic pulmonary fibrosis (IPF) is a disease with very poor prognosis and no curative therapies. The G protein-coupled, calcium/cation-sensing receptor (CaSR) is activated by environmental pollutants and by arginine-derived polyamines, which are thought to play a role in IPF. Whether the CaSR is involved in the pathogenesis of pulmonary fibrosis is unknown. Objective: To investigate the CaSR as a novel drug target for the treatment of pulmonary fibrosis (PF). Methods and results: CaSR protein expression is found in the airway epithelium in the neuroepithelial bodies of the healthy and IPF human lung. Expression of arginine pathway-linked polyamines is increased in PF patient saliva samples compared to non-PF patients. Arginine pathway metabolites, ornithine and spermine, activate the CaSR in primary normal human lung fibroblasts (NHLF), effects prevented by CaSR antagonism using the calcilytic NPS2143. In NHLF calcilytic also reversed the pro-fibrotic effects of exogenous TGFβ1 administration on Rho kinase and αSMA expression, proliferation, collagen production and IL-8 secretion. Targeted CaSR ablation from fibroblasts and smooth muscle cells protects mice from spontaneously occurring, age-related lung fibrosis. Conclusions: Sustained CaSR activation in the lung drives pro-fibrotic processes, which can be reversed by calcilytic. Pharmacological and genetic CaSR blockade reduce both TGFβ1-induced and naturally occurring pro-fibrotic changes. This work provides the scientific rationale for developing inhaled calcilytics as novel therapeutics for IPF.

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High levels of IL-6 and IL-8 characterize early-on idiopathic pulmonary fibrosis acute exacerbations

Cited by 131 publications

References 16 publications

Acute Exacerbation of Interstitial Lung Disease in Adult Patients With Idiopathic Inflammatory Myopathies: A Retrospective Case-Control Study

Acute Exacerbation of Interstitial Lung Disease in Adult Patients With Idiopathic Inflammatory Myopathies: A Retrospective Case-Control Study

Anlotinib attenuated bleomycin-induced pulmonary fibrosis via the TGF-β1 signalling pathway

Calcium-sensing receptor antagonism as a novel therapeutic for pulmonary fibrosis

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