scholarly journals Systemic Inflammation during and after Bronchiectasis Exacerbations: Impact of Pseudomonas aeruginosa

2020 ◽  
Vol 9 (8) ◽  
pp. 2631
Author(s):  
Rosario Menéndez ◽  
Raúl Méndez ◽  
Isabel Amara-Elori ◽  
Soledad Reyes ◽  
Beatriz Montull ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Tumor Necrosis Factor ◽  
Systemic Inflammation ◽  
Tumor Necrosis ◽  
High Sensitivity ◽  
Severity Index ◽  
Proinflammatory Response ◽  
Necrosis Factor Alpha ◽  
Structural Disease ◽  
Necrosis Factor

Bronchiectasis is a chronic structural disease associated with exacerbations that provoke systemic inflammation. We aimed to evaluate the systemic acute proinflammatory cytokine and its biomarker profiles during and after exacerbations and its relationship with the severity of episode, microbiological findings, and the bronchiectasis severity index. This prospective observational study compared exacerbation and stable groups. Cytokine (interleukins (IL)-17a, IL-1β, IL-6, IL 8; tumor necrosis factor-alpha (α)) and high-sensitivity C-reactive protein (hsCRP) levels were determined by multiplex analysis on days 1, 5, 30, and 60 in the exacerbation group and on day 1 in the stable group. We recruited 165 patients with exacerbations, of which 93 were severe (hospitalized). Proinflammatory systemic IL-17a, IL-1β, IL-8, and tumor necrosis factor-α levels increased similarly on days 1 and 5 in severe and non-severe episodes, but on day 30, IL-17a, IL-8, and IL-6 levels were only increased for severe exacerbations. The highest IL-17a level occurred in patients with chronic plus the acute isolation of Pseudomonas aeruginosa. At 30 days, severe exacerbations were independently associated with higher levels of IL-17 (Odds ratio (OR) 4.58), IL-6 (OR 4.89), IL-8 (OR 3.08), and hsCRP (OR 6.7), adjusted for age, the bronchiectasis severity index, and treatment duration. Exacerbations in patients with chronic P. aeruginosa infection were associated with an increase in IL-17 and IL-6 at 30 days (ORs 7.47 and 3.44, respectively). Severe exacerbations elicit a higher systemic proinflammatory response that is sustained to day 30. Patients with chronic P. aeruginosa infection had impaired IL-17a reduction. IL-17a could be a useful target for measuring systemic inflammation.

scholarly journals Pseudomonas aeruginosa Slime Glycolipoprotein Is a Potent Stimulant of Tumor Necrosis Factor Alpha Gene Expression and Activation of Transcription Activators Nuclear Factor κB and Activator Protein 1 in Human Monocytes

2003 ◽  
Vol 71 (8) ◽  
pp. 4614-4622 ◽  
Author(s):  
George Lagoumintzis ◽  
Myrto Christofidou ◽  
George Dimitracopoulos ◽  
Fotini Paliogianni
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Activator Protein 1 ◽  
Human Monocytes ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Viable Bacteria ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Pseudomonas aeruginosa, an opportunistic pathogen, causes infections associated with a high incidence of morbidity and mortality in immunocompromised hosts. Production of tumor necrosis factor alpha (TNF-α), primarily by cells of monocytic lineage, is a crucial event in the course of these infections. During in vivo infections with P. aeruginosa, both lipopolysaccharide (LPS) and extracellular slime glycolipoprotein (GLP) produced by mucoid and nonmucoid strains are released. In the present study, we sought to explore the relative contributions of these two bacterial products to TNF-α production by human monocytes. To this end, fresh human monocytes and THP-1 human monocytic cells were stimulated with P. aeruginosa LPS or GLP. GLP was found to be a more potent stimulus for TNF-α production (threefold higher) by human monocytes than LPS. Moreover, its effect was comparable to that of viable bacteria. Quantitative mRNA analysis revealed predominantly transcriptional regulation. Electrophoretic mobility shift assays and transfection assays demonstrated activation of NF-κB and activator protein 1 (AP-1). NF-κB activation by GLP was rapid and followed the same time course as that by viable bacteria, suggesting that bacteria could directly activate NF-κB through GLP. Moreover P. aeruginosa GLP induced the formation of AP-1 complex with delayed kinetics compared with NF-κB but much more efficiently than the homologous LPS. These results identify GLP as the most important stimulant for TNF-α production by human monocytes. Activation of NF-κB and AP-1 by P. aeruginosa GLP may be involved not only in TNF-α induction but also in many of the inflammatory responses triggered in the course of infection with P. aeruginosa.

scholarly journals Lipopolysaccharide (LPS) from Burkholderia cepacia Is More Active than LPS from Pseudomonas aeruginosa and Stenotrophomonas maltophilia in Stimulating Tumor Necrosis Factor Alpha from Human Monocytes

1999 ◽  
Vol 67 (3) ◽  
pp. 1505-1507 ◽  
Author(s):  
Susu M. Zughaier ◽  
Henry C. Ryley ◽  
Simon K. Jackson
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Burkholderia Cepacia ◽  
Stenotrophomonas Maltophilia ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Whole cells and lipopolysaccharides (LPSs) extracted fromBurkholderia cepacia, Pseudomonas aeruginosa,Stenotrophomonas maltophilia, and Escherichia coli were compared in their ability to stimulate tumor necrosis factor alpha (TNF-α) from the human monocyte cell line MonoMac-6.B. cepacia LPS, on a weight-for-weight basis, was found to have TNF-α-inducing activity similar to that of LPS from E. coli, which was approximately four- and eightfold greater than the activity of LPSs from P. aeruginosa and S. maltophilia, respectively. The LPS-stimulated TNF-α production from monocytes was found to be CD14 dependent. These results suggest that B. cepacia LPS might play a role in the pathogenesis of inflammatory lung disease in cystic fibrosis, and in some patients it might be responsible, at least in part, for the sepsis-like cepacia syndrome.

scholarly journals Chitinase 3-Like 1 (Chil1) Regulates Survival and Macrophage-Mediated Interleukin-1β and Tumor Necrosis Factor Alpha during Pseudomonas aeruginosa Pneumonia

2016 ◽  
Vol 84 (7) ◽  
pp. 2094-2104 ◽  
Author(s):  
Chad R. Marion ◽  
Jianmiao Wang ◽  
Lokesh Sharma ◽  
Ashley Losier ◽  
Wei Lui ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Tumor Necrosis Factor ◽  
Host Resistance ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Factor Alpha ◽  
Host Tolerance ◽  
Deficient Mice ◽  
Necrosis Factor

Pseudomonas aeruginosacauses hospital-acquired pneumonia and is associated with high mortality. An effective response to such an infection includes efficient clearance of pathogenic organisms while limiting collateral damage from the host inflammatory response, known as host resistance and host tolerance, respectively.P. aeruginosaexpresses a type III secretion system (T3SS) needle complex that induces NLRC4 (NOD-like receptor C4) activation, interleukin-1β (IL-1β) production, and host tissue damage. Chitinase 3-like-1 (Chil1) is expressed during infection and binds to its receptor, IL-13 receptor α2 (IL-13Rα2), to regulate the pathogen-host response duringStreptococcus pneumoniaeinfection, but the role Chil1 plays in balancing the host resistance and host tolerance duringP. aeruginosapneumonia is not known. We conducted experiments using C57BL/6 mice with or without a genetic deficiency of Chil1 and demonstrated that Chil1-deficient mice succumb toP. aeruginosainfection more rapidly than the wild type (WT). The decreased survival time in infected Chil1-deficient mice is associated with more neutrophils recruited to the airways, more lung parenchymal damage, and increased pulmonary consolidation while maintaining equivalent bacterial killing compared to WT mice. Infected Chil1-deficient mice and bone marrow-derived macrophages (BMDMs) from Chil1-deficient mice have increased production of tumor necrosis factor alpha (TNF-α) and IL-1β compared to infected WT mice and macrophages. Infection of Chil1-deficient BMDMs with non-NLRC4-triggeringP. aeruginosa, which is deficient in the T3SS needle complex, did not alter the excessive IL-1β production compared to BMDMs from WT mice. The addition of recombinant Chil1 decreases the excessive IL-1β production but only partially rescues stimulated BMDMs from IL-13Rα2-deficient mice. Our data provide mechanistic insights into how Chil1 regulatesP. aeruginosa-induced host responses.

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