How Glucocorticoids Affect the Neutrophil Life

Ronchetti, Simona; Migliorati, Graziella; Gentili, M; Riccardi, Carlo

doi:10.3390/ijms19124090

Cited by 162 publications

(166 citation statements)

References 86 publications

(90 reference statements)

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“…Consistently, as previously reported, steroids can induce increased absolute neutrophil count (ANC) [ 19 , 20 , 21 ], and it has been even associated with the polarization of macrophages to M2 macrophages, with pro-tumoral functions [ 22 ]. Thus, the global impact of steroids on the immune context of the patients should be further explored.…”

Section: Discussionsupporting

confidence: 73%

Impact of Intercurrent Introduction of Steroids on Clinical Outcomes in Advanced Non-Small-Cell Lung Cancer (NSCLC) Patients under Immune-Checkpoint Inhibitors (ICI)

Giglio

Mezquita

Auclin

et al. 2020

Cancers

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Background: Baseline steroids before ICI have been associated with poor outcomes, particularly when introduced due to cancer symptoms. Methods: Retrospective analysis of advanced NSCLC patients treated with ICI. We collected the use of intercurrent steroids (≥10 mg of prednisone-equivalent) within the first eight weeks of ICI. We correlated steroid use with patient outcomes according to the indications. Results: 413 patients received ICI, 299 were steroids-naïve at baseline. A total of 49 patients received intercurrent steroids (16%), of whom 38 for cancer-related symptoms and 11 for other indications, such as immune-related events. Overall, median (m) progression-free survival (PFS) was 1.9 months (mo.) [95% CI, 1.8-2.4] and overall survival (OS) 10 mo. [95% CI, 8.1–12.9]. Intercurrent steroids under ICI correlated with a shorter PFS/OS (1.3 and 2.3 mo. respectively, both p < 0.0001). Intercurrent steroids for cancer-related symptoms correlated with poorest mPFS [1.1 mo.; 95% CI, 0.9–1.5] and mOS [1.9 mo.; 95%CI, 1.5–2.4; p < 0.0001)]. No mOS and mPFS differences were found between cancer-unrelated-steroid group and no-steroid group. Steroid use for cancer-related symptoms was an independent prognostic factor for poor PFS [HR 2.64; 95% CI, 1.2–5.6] and OS [HR 4.53; 95% CI, 1.8–11.1], both p < 0.0001. Conclusion: Intercurrent steroids during ICI had no detrimental prognostic impact if the indication was unrelated to cancer symptoms.

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Section: Discussionsupporting

confidence: 73%

Impact of Intercurrent Introduction of Steroids on Clinical Outcomes in Advanced Non-Small-Cell Lung Cancer (NSCLC) Patients under Immune-Checkpoint Inhibitors (ICI)

Giglio

Mezquita

Auclin

et al. 2020

Cancers

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“…The relationship between glucocorticoids and T-lymphocytes is complex, but there appears to be a consensus in the literature that glucocorticoids lead to thymocyte apoptosis, with subsequent decrease in immature T-cell counts [38][39][40][41] and skewing of the T-cell response toward Th2 [41][42][43] . In addition, we hypothesize that corticosteroid treatment in mice reduced migration of neutrophils from the blood into the lungs, coupled with reductions in superoxide and reactive oxygen species, which may have allowed M. abscessus to proliferate unimpaired [44][45][46][47] . No animal model is able to comprehensively simulate all aspects of human infection and pathology, nor does any one model meet all investigative goals within.…”

Section: Discussionmentioning

confidence: 99%

A mouse model of pulmonary Mycobacteroides abscessus infection

Maggioncalda

Story-Roller

Mylius

et al. 2020

Sci Rep

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there is no preclinical mouse model to investigate pulmonary Mycobacteroides abscessus (formerly Mycobacterium abscessus) infection in an immunocompetent mouse strain, especially in the context of antibiotic testing and regimen development. We developed a mouse model of pulmonary M. abscessus infection using the aerosolized route of infection that leads to an increase in bacterial burden postimplantation and develops pathology as a result. in this mouse model, treatment with corticosteroid allows for initial proliferation and sustained M. abscessus pulmonary infection and permits evaluation of efficacies of antibiotics. Administration of corticosteroids that permitted higher levels of bacterial burden in the lungs were more likely to have pathology. treatment of mice with antibiotics administered intranasally or subcutaneously significantly reduced lung M. abscessus burden. in addition to the reference strain, independent clinical isolates of M. abscessus also readily establish infection and proliferate in the lungs of mice in this model. In the setting of structural lung conditions such as cystic fibrosis, bronchiectasis, and COPD, Mycobacteroides abscessus (formerly Mycobacterium abscessus) can cause chronic pulmonary infection 1,2 that is often incurable and associated with rapid lung function decline 3-5. There is a current interest in developing new drugs and regimens to treat M. abscessus infection, as the cure rate with existing antibiotics is only 30-50% 6. While there have been many exciting demonstrations of in vitro potencies of antibiotics against M. abscessus 7-13 , it has also been established that potency observed in vitro for M. abscessus often does not translate to an equivalent clinical efficacy in the case of pulmonary infections 3. This highlights the need for a preclinical animal model to evaluate experimental antibiotics. A mammalian model that recapitulates aerosol infection leading to progressive M. abscessus burden and development of lung pathology as observed in human disease would facilitate preclinical studies of antibiotic efficacy and M. abscessus genetic determinants for virulence. In investigations of Mycobacterium tuberculosis (M. tuberculosis), several studies have demonstrated that aerosol infected C3HeB/FeJ mice closely mimic human pulmonary pathology 14-17. However, when infected with M. abscessus, these mice are able to clear the infection 18. Other immunocompetent mouse strains also clear the infection over time, although certain genetically manipulated immunocompromised strains were able to maintain bacterial burden 19-22. This is a compromise in favor of perpetuating the infection, but at a loss of immune cells and inflammatory markers normally observed in response to infection. Therefore, as mice are unable to mount an immune response, this precludes evaluation of critical aspects of host-pathogen interactions and pathology development that may impact efficacy of antibiotic treatments. We hypothesized that transient pharmacologically-induced immune suppression of immunoco...

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“…Hence, corticosteroids have proinflammatory effects in neutrophils. Corticosteroids are generally thought to weakly suppress neutrophilic inflammation, although several research groups reported them to inhibit the neutrophil respiratory burst and interfere with neutrophil recruitment ( Strausbaugh and Rosen, 2001 ; Ronchetti et al, 2018 ; Ricci et al, 2019 ). For instance, corticosteroids do not improve neutrophilic inflammation in corticosteroid-resistant asthma or COPD ( Yang et al, 2012 ; Ronchetti et al, 2018 ).…”

Section: Drugs Targeting Neutrophils For Covid-19 Associated Ardsmentioning

confidence: 99%

Targeting Neutrophils to Treat Acute Respiratory Distress Syndrome in Coronavirus Disease

et al. 2020

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This review describes targeting neutrophils as a potential therapeutic strategy for acute respiratory distress syndrome (ARDS) associated with coronavirus disease 2019 (COVID-19), a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Neutrophil counts are significantly elevated in patients with COVID-19 and significantly correlated with disease severity. The neutrophil-to-lymphocyte ratio can serve as a clinical marker for predicting fatal complications related to ARDS in patients with COVID-19. Neutrophil-associated inflammation plays a critical pathogenic role in ARDS. The effector functions of neutrophils, acting as respiratory burst oxidants, granule proteases, and neutrophil extracellular traps, are linked to the pathogenesis of ARDS. Hence, neutrophils can not only be used as pathogenic markers but also as candidate drug targets for COVID-19 associated ARDS.

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How Glucocorticoids Affect the Neutrophil Life

Cited by 162 publications

References 86 publications

Impact of Intercurrent Introduction of Steroids on Clinical Outcomes in Advanced Non-Small-Cell Lung Cancer (NSCLC) Patients under Immune-Checkpoint Inhibitors (ICI)

Impact of Intercurrent Introduction of Steroids on Clinical Outcomes in Advanced Non-Small-Cell Lung Cancer (NSCLC) Patients under Immune-Checkpoint Inhibitors (ICI)

A mouse model of pulmonary Mycobacteroides abscessus infection

Targeting Neutrophils to Treat Acute Respiratory Distress Syndrome in Coronavirus Disease

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