Anti-TNFα therapy in inflammatory lung diseases

Malaviya, Rama; Laskin, Jeffrey D.; Laskin, Debra L.

doi:10.1016/j.pharmthera.2017.06.008

Cited by 190 publications

(153 citation statements)

References 164 publications

(198 reference statements)

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“…IL-1α and IL-1β activate a common IL-1 receptor (IL-1R), and seem via inflammation to be involved in a range of pathological processes [34][35][36]. In addition, TNF-α appears to be critical in the onset of pro-inflammatory signalling in silica-induced pathologies [37,38]. In contrast to larger crystalline silica particles that presumably exert their effects via such pro-inflammatory mediators, small SiNPs may translocate across the airway barrier to the systematic circulation, and potentially exert direct effects in secondary organs [39,40].…”

Section: Introductionmentioning

confidence: 99%

Pro-inflammatory effects of crystalline- and nano-sized non-crystalline silica particles in a 3D alveolar model

et al. 2020

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Background: Silica nanoparticles (SiNPs) are among the most widely manufactured and used nanoparticles. Concerns about potential health effects of SiNPs have therefore risen. Using a 3D tri-culture model of the alveolar lung barrier we examined effects of exposure to SiNPs (Si10) and crystalline silica (quartz; Min-U-Sil) in the apical compartment consisting of human alveolar epithelial A549 cells and THP-1-derived macrophages, as well as in the basolateral compartment with Ea.hy926 endothelial cells. Inflammation-related responses were measured by ELISA and gene expression. Results: Exposure to both Si10 and Min-U-Sil induced gene expression and release of CXCL8, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α) and interleukin-1β (IL-1β) in a concentration-dependent manner. Cytokine/chemokine expression and protein levels were highest in the apical compartment. Si10 and Min-U-Sil also induced expression of adhesion molecules ICAM-1 and E-selectin in the apical compartment. In the basolateral endothelial compartment we observed marked, but postponed effects on expression of all these genes, but only at the highest particle concentrations. Geneexpressions of heme oxygenase-1 (HO-1) and the metalloproteases (MMP-1 and MMP-9) were less affected. The IL-1 receptor antagonist (IL-1RA), markedly reduced effects of Si10 and Min-U-Sil exposures on gene expression of cytokines and adhesion molecules, as well as cytokine-release in both compartments. Conclusions: Si10 and Min-U-Sil induced gene expression and release of pro-inflammatory cytokines/adhesion molecules at both the epithelial/macrophage and endothelial side of a 3D tri-culture. Responses in the basolateral endothelial cells were only induced at high concentrations, and seemed to be mediated by IL-1α/β released from the apical epithelial cells and macrophages.

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Section: Introductionmentioning

confidence: 99%

Pro-inflammatory effects of crystalline- and nano-sized non-crystalline silica particles in a 3D alveolar model

et al. 2020

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“…We know that TNFα is overexpressed also in severe respiratory distress syndrome. 9 In this way, current treatment with adalimumab not only could not be a risk factor for both severity of pulmonary disease and recurrence of the intestinal disease in patients with CD infected by covid-19, but also could reinforce the hypothesis to use adalimumab in treating at least some of the infected people. 2 Of course, the questions raised by this case have to be addressed by the large epidemiological studies currently ongoing.…”

Section: Covid-19 Infection In Crohn's Disease Under Treatment With Amentioning

confidence: 85%

COVID-19 infection in Crohn’s disease under treatment with adalimumab

Tursi

Angarano

Monno

et al. 2020

Gut

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“…We found the non-survivors of ARDS had higher levels of phenylacetylglutamine than survivors, the mechanisms underlying may be related to the roles of phenylacetylglutamine in modulating platelets and thrombosis. In the last decades, a broad range of drug therapies emerged for improving ARDS, but none showed efficacy in phase II and III trials [26][27][28][29][30][31]. Given the high mortality rate of ARDS, even a small improvement can save many lives.…”

Section: Discussionmentioning

confidence: 99%

Increased mortality of acute respiratory distress syndrome was associated with high levels of plasma phenylalanine

Pan

et al. 2020

Respir Res

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Background: There is a dearth of drug therapies available for the treatment of acute respiratory distress syndrome (ARDS). Certain metabolites play a key role in ARDS and could serve as potential targets for developing therapies against this respiratory disorder. The present study was designed to determine such "functional metabolites" in ARDS using metabolomics and in vivo experiments in a mouse model.Methods: Metabolomic profiles of blood plasma from 42 ARDS patients and 28 healthy controls were captured using Ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) assay. Univariate and multivariate statistical analysis were performed on metabolomic profiles from blood plasma of ARDS patients and healthy controls to screen for "functional metabolites", which were determined by variable importance in projection (VIP) scores and P value. Pathway analysis of all the metabolites was performed. The mouse model of ARDS was established to investigate the role of "functional metabolites" in the lung injury and mortality caused by the respiratory disorder. Results: The metabolomic profiles of patients with ARDS were significantly different from healthy controls, difference was also observed between metabolomic profiles of the non-survivors and the survivors among the ARDS patient pool. Levels of Phenylalanine, D-Phenylalanine and Phenylacetylglutamine were significantly increased in non-survivors compared to the survivors of ARDS. Phenylalanine metabolism was the most notably altered pathway between the non-survivors and survivors of ARDS patients. In vivo animal experiments demonstrated that high levels of Phenylalanine might be associated with the severer lung injury and increased mortality of ARDS. Conclusion: Increased mortality of acute respiratory distress syndrome was associated with high levels of plasma Phenylalanine.

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Anti-TNFα therapy in inflammatory lung diseases

Cited by 190 publications

References 164 publications

Pro-inflammatory effects of crystalline- and nano-sized non-crystalline silica particles in a 3D alveolar model

Pro-inflammatory effects of crystalline- and nano-sized non-crystalline silica particles in a 3D alveolar model

COVID-19 infection in Crohn’s disease under treatment with adalimumab

Increased mortality of acute respiratory distress syndrome was associated with high levels of plasma phenylalanine

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