Corticosteroids for Treating Sepsis in Children and Adults

Cooper, Adam S.

doi:10.4037/ccn2020588

Cited by 2 publications

(2 citation statements)

References 3 publications

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“…In the bleomycin and LPS/TNF‐α models, no infectious agent was used, and so a comparable effect of anti‐inflammatory drugs like dexamethasone would have been expected, which was also demonstrated with preliminary data 8,43 . However, albeit being indispensable anti‐inflammatory drugs, corticosteroids impose severe risks of opportunistic or exacerbated infections and have long been considered controversial in the context of acute infectious inflammation, like sepsis 45,46 . One important consequence of corticosteroids is the disadvantageous effect on T cells, where dexamethasone suppresses T cell proliferation and differentiation 47 .…”

Section: Suppressing Inflammation Without Suppressing Lymphocytesmentioning

confidence: 89%

“…8,43 However, albeit being indispensable anti-inflammatory drugs, corticosteroids impose severe risks of opportunistic or exacerbated infections and have long been considered controversial in the context of acute infectious inflammation, like sepsis. 45,46 One important consequence of corticosteroids is the disadvantageous effect on T cells, where dexamethasone suppresses T cell proliferation and differentiation. 47 Interestingly, OGG1 inhibition with TH5487 did not suppress T cells in concentrations relevant for immunosuppression.…”

Section: Suppressing Inflammation Without Suppressing Lymphocytesmentioning

confidence: 99%

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Targeting the DNA repair enzymes MTH1 and OGG1 as a novel approach to treat inflammatory diseases

Karsten

2022

Basic Clin Pharma Tox

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Autoimmune diseases and acute inflammation like sepsis cause significant morbidity and disability globally, and new targeted therapies are urgently needed. DNA repair and reactive oxygen species (ROS) pathways have long been investigated as targets for cancer treatment, but their role in immunological research has been limited. In this MiniReview, we discuss the DNA repair enzymes MTH1 and OGG1 as targets to treat both T cell-driven diseases and acute inflammation. The MiniReview is based on a PhD thesis where both enzymes were investigated with cell and animal models. For MTH1, we found that its inhibition selectively kills activated T cells without being toxic to resting cells or other tissues. MTH1 inhibition also had an alleviating role in disease models of psoriasis and multiple sclerosis. We further identified a novel MTH1 low ROS low phenotype among activated T cells. Regarding OGG1, we demonstrated a mechanism of action of the OGG1 inhibitor TH5487, which prevents the assembly of pro-inflammatory transcription factors and mitigates acute airway infection in mouse models of pneumonia. Hence, we propose both enzymes to be promising novel targets to treat inflammation and suggest that redox and DNA repair pathways could be useful targets for future immunomodulating therapies.

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Section: Suppressing Inflammation Without Suppressing Lymphocytesmentioning

confidence: 89%

Section: Suppressing Inflammation Without Suppressing Lymphocytesmentioning

confidence: 99%

Targeting the DNA repair enzymes MTH1 and OGG1 as a novel approach to treat inflammatory diseases

Karsten

2022

Basic Clin Pharma Tox

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Shared inflammatory pathways and therapeutic strategies in COVID-19 and cancer immunotherapy

Iovino

Hill

Gnjatic

et al. 2021

J Immunother Cancer

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COVID-19, the syndrome caused by the infection with SARS-CoV-2 coronavirus, is characterized, in its severe form, by interstitial diffuse pneumonitis and acute respiratory distress syndrome (ARDS). ARDS and systemic manifestations of COVID-19 are mainly due to an exaggerated immune response triggered by the viral infection. Cytokine release syndrome (CRS), an inflammatory syndrome characterized by elevated levels of circulating cytokines, and endothelial dysfunction are systemic manifestations of COVID-19. CRS is also an adverse event of immunotherapy (IMTX), the treatment of diseases using drugs, cells, and antibodies to stimulate or suppress the immune system. Graft-versus-host disease complications after an allogeneic stem cell transplant, toxicity after the infusion of chimeric antigen receptor-T cell therapy and monoclonal antibodies can all lead to CRS. It is hypothesized that anti-inflammatory drugs used for treatment of CRS in IMTX may be useful in reducing the mortality in COVID-19, whereas IMTX itself may help in ameliorating effects of SARS-CoV-2 infection. In this paper, we focused on the potential shared mechanisms and differences between COVID-19 and IMTX-related toxicities. We performed a systematic review of the clinical trials testing anti-inflammatory therapies and of the data published from prospective trials. Preliminary evidence suggests there might be a benefit in targeting the cytokines involved in the pathogenesis of COVID-19, especially by inhibiting the interleukin-6 pathway. Many other approaches based on novel drugs and cell therapies are currently under investigation and may lead to a reduction in hospitalization and mortality due to COVID-19.

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Corticosteroids for Treating Sepsis in Children and Adults

Cited by 2 publications

References 3 publications

Targeting the DNA repair enzymes MTH1 and OGG1 as a novel approach to treat inflammatory diseases

Targeting the DNA repair enzymes MTH1 and OGG1 as a novel approach to treat inflammatory diseases

Shared inflammatory pathways and therapeutic strategies in COVID-19 and cancer immunotherapy

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