Comparative Study of the Levels of IL-1β, IL-4, IL-8, TNFα, and IFNγ in Stable Course and Exacerbation of Chronic Obstructive Pulmonary Disease of Varying Severity

Kubysheva, Nailya; Postnikova, Larisa; Soodaeva, S K; Novikov, D V; Eliseeva, T.I.; Novikov, V. V.; Караулов, А. В.

doi:10.1007/s10517-022-05622-z

Cited by 7 publications

(3 citation statements)

References 7 publications

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“…Finally, IL-4 has been shown to be involved in the differentiation of CD4+ T cells into TH2 cells and in the activation of myeloid cells, resulting in the stimulation of wound healing and suppression of harmful over-inflammation [ 39 ]. In accordance with our data, IL-4 has already been shown to be upregulated in COPD patients and to correlate with disease severity [ 40 ]. Interestingly, we showed here that IL-4 levels were decreased in our BCO population.…”

Section: Discussionsupporting

confidence: 92%

Adiponectin Increase in Patients Affected by Chronic Obstructive Pulmonary Disease with Overlap of Bronchiectasis

Nigro

Mosella

Daniele

et al. 2023

Life

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Chronic obstructive pulmonary disease (COPD) is characterized by respiratory symptoms and non-reversible airflow limitation with recurrent episodes of acute exacerbations. The concurrent presence of bronchiectasis in patients with COPD is associated with reduced respiratory function as well as increased exacerbation risk. Adiponectin is a promising biomarker in COPD, as greater high molecular weight (HMW) oligomer levels have been observed among COPD patients. Here, we investigate adiponectin levels in two groups of COPD patients characterized by the presence or absence of bronchiectasis (BCO), comparing both groups to healthy controls. We evaluated serum adiponectin levels in COPD patients, those with BCO, and healthy subjects and characterized the pattern of circulating adiponectin oligomers. We found that forced volume capacity % (FVC%) and forced expiratory volume % (FEV1%) were lower for BCO patients than for COPD patients. COPD patients had higher levels of adiponectin and its HMW oligomers than healthy controls. Interestingly, BCO patients had higher levels of adiponectin than COPD patients. We showed that expression levels of IL-2, -4, and -8, IFN-γ, and GM-CSF were significantly higher in BCO patients than in healthy controls. Conversely, IL-10 expression levels were lower in BCO patients. Our data suggest that the increased levels of adiponectin detected in the cohort of BCO patients compared to those in COPD patients without bronchiectasis might be determined by their worse airway inflammatory state. This hypothesis suggests that adiponectin could be considered as a biomarker to recognize advanced COPD patients with bronchiectasis.

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Section: Discussionsupporting

confidence: 92%

Adiponectin Increase in Patients Affected by Chronic Obstructive Pulmonary Disease with Overlap of Bronchiectasis

Nigro

Mosella

Daniele

et al. 2023

Life

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“…CHF6297, in a dry powder formulation blended with lactose, proved to have suitable lung retention after inhalation delivery in rats and was very effective in reducing LPS-induced neutrophil influx in rat BALF, confirming the rationale for inhibiting p38α in inflamed neutrophilic airways. The robust anti-inflammatory effect of CHF6297 was also confirmed in another model of acute pulmonary inflammation induced by the instillation of IL-1β, a proinflammatory cytokine associated with inflammasome activation and elevated during acute COPD exacerbations ( Kubysheva et al, 2022 ), as well as during the hyperinflammatory response occurring in severe acute respiratory syndrome driven by SARS-CoV-2 ( Gilroy et al, 2021 ). Airway inflammation in COPD, especially during acute exacerbations, is partially insensitive/resistant to inhaled corticosteroids (ICS), thus limiting the efficacy of current ICS-based therapies ( Barnes, 2013 ).…”

Section: Discussionmentioning

confidence: 75%

CHF6297: a novel potent and selective p38 MAPK inhibitor with robust anti-inflammatory activity and suitable for inhaled pulmonary administration as dry powder

Martucci,

Allen,

Moretto

et al. 2024

Front. Pharmacol.

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Inhibition of p38 mitogen-activated protein kinase (MAPKs) is a potential therapeutic approach for the treatment of acute and chronic pulmonary inflammatory conditions. Here, we report the in vitro and in vivo characterization of the anti-inflammatory effects of CHF6297, a novel potent and selective p38α inhibitor designed for inhalation delivery as a dry powder formulation. CHF6297 has been proven to inhibit p38α enzymatic activity with sub-nanomolar potency (IC50 = 0.14 ± 0.06 nM), with >1,000-fold selectivity against p38γ and p38δ. In human peripheral blood mononuclear cells (PBMCs) stimulated with lipopolysaccharides (LPS), as well as in human bronchial epithelial cells (BEAS2B) stimulated with TNF-α or cigarette smoke extract (CSE), CHF6297 inhibited interleukin (IL)-8 release with low nanomolar potency. CHF6297 administered to rats by using a nose-only inhalation device as a micronized dry powder formulation blended with lactose dose-dependently inhibited the LPS-induced neutrophil influx in the bronchoalveolar lavage fluid (BALF). CHF6297 administered intratracheally to rats dose-dependently counteracted the IL-1β (0.3 mg/kg)-induced neutrophil influx (ED50 = 0.22 mg/kg) and increase in IL-6 levels (ED50 = 0.82 mg/kg) in the BALF. In mice exposed to tobacco smoke (TS), CHF6297, administered intranasally (i.n.) for 4 days at 0.03 or 0.3 mg/kg, dose-dependently inhibited the corticosteroid-resistant TS-induced neutrophil influx in the BALF. In a murine house dust mite (HDM) model of asthma exacerbated by influenza virus A (IAV) (H3N3), CHF6297 (0.1 mg/kg, i.n.) significantly decreased airway neutrophilia compared to vehicle-treated IAV/HDM-challenged mice. When CHF6297, at a dose ineffective per se (0.03 mg/kg), was added to budesonide, it augmented the anti-inflammatory effects of the steroid. Overall, CHF6297 effectively counteracted lung inflammation in experimental models where corticosteroids exhibit limited anti-inflammatory activity, suggesting a potential for the treatment of acute exacerbations associated with chronic obstructive pulmonary disease (COPD) and asthma, acute lung injury (ALI), and viral-induced hyperinflammation.

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“…Previous investigations on systemic inflammation in COPD have only assessed a small number of protein markers, such as TNF-, IL-1, IL-6, C-reactive protein (CRP) and fibrinogen [15][16][17][18][19]. Some studies showed that stable COPD patients with simultaneously elevated levels of CRP, fibrinogen and leucocyte counts had an increased risk of suffering frequent exacerbations [15,16].…”

Section: Previous Studiesmentioning

confidence: 99%

COPD: systemic proteomic profiles in frequent and infrequent exacerbators

Enríquez-Rodríguez,

Casadevall,

Faner

et al. 2024

ERJ Open Res

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BackgroundSome patients with chronic obstructive pulmonary disease (COPD) suffer frequent exacerbations (FE). We hypothesized that their systemic proteomic profile would be different from that of non-frequent exacerbators (NFE).ObjectivesTo contrast the systemic proteomic profile in FEversusNFE. As a reference, we also determined the systemic proteomic profile of healthy controls (HC) and COPD patients during an actual episode of exacerbation (AE).MethodsIn the analysis we included 40 clinically stable COPD patients (20 FE and 20 NFE), 20 HC and 10 AE patients. Their plasma samples were analysed by combining two complementary proteomic approaches: label-free liquid chromatography-tandem mass spectrometry and multiplex immunoassays. Gene Ontology annotation, pathway enrichment and network analyses were used to investigate molecular pathways associated with differentially abundant proteins-peptides (DAPs).ResultsCompared with HC, we identified 40 DAPs in FE, 10 in NFE and 63 in AE. Also compared to HC, pathway functional and protein-protein network analyses revealed dysregulation of inflammatory responses involving innate and antibody-mediated immunity in COPD, particularly in the FE group, as well as during an AE episode. Besides, we only identified alterations in the complement and coagulation cascades in AE.ConclusionThere are specific plasma proteome profiles associated with FE, which are partially shared with findings observed during AE, albeit others are uniquely present during the actual episode of AE.

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Comparative Study of the Levels of IL-1β, IL-4, IL-8, TNFα, and IFNγ in Stable Course and Exacerbation of Chronic Obstructive Pulmonary Disease of Varying Severity

Cited by 7 publications

References 7 publications

Adiponectin Increase in Patients Affected by Chronic Obstructive Pulmonary Disease with Overlap of Bronchiectasis

Adiponectin Increase in Patients Affected by Chronic Obstructive Pulmonary Disease with Overlap of Bronchiectasis

CHF6297: a novel potent and selective p38 MAPK inhibitor with robust anti-inflammatory activity and suitable for inhaled pulmonary administration as dry powder

COPD: systemic proteomic profiles in frequent and infrequent exacerbators

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