New Insights on Effects of Glucocorticoids in Patients With SARS-CoV-2 Infection

Shacham, Elena Chertok; Ishay, Avraham

doi:10.1016/j.eprac.2022.07.006

Cited by 5 publications

(1 citation statement)

References 76 publications

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“…JPET Fast Forward. Published on January 11, 2023as DOI: 10.1124 at ASPET Journals on January 15, 2023 jpet.aspetjournals.org Downloaded from 7 coding adhesion molecules and by impacting proliferation and degradation of immune cells (Chertok Shacham and Ishay, 2022). In addition, synthetic glucocorticoids suppress the production of endogenous CS, both in humans and in animals, by inhibiting the hypothalamic-pituitary-adrenal (HPA) axis responsible for regulation of production of cortisol in humans and corticosterone (CST) in rats (Mager et al, 2003;Yao et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic/Pharmacodynamic Modeling of Dexamethasone Anti-Inflammatory and Immunomodulatory Effects in LPS-Challenged Rats: A Model for Cytokine Release Syndrome

Świerczek

Jusko

2023

The Journal of Pharmacology and Experimental Therapeutics

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IC 50 -Concentration resulting in 50% of the maximum inhibition IL-6 -Interleukin 6 I max -Maximum inhibition iNOS -Inducible nitric oxide synthase IP -Intraperitoneal LC-MS/MS -Liquid chromatography tandem-mass spectrometry LLOQ -Lower limit of quantification LPS -Lipopolysaccharide mPBPK/PD -Minimal physiologically-based pharmacokinetic/pharmacodynamic MRM -Multiple reaction monitoring NF-κB -Nuclear factor kappa-light-chain-enhancer of activated B cells NO -Nitric oxide PD -Pharmacodynamic PK -Pharmacokinetic PK/PD -Pharmacokinetic/pharmacodynamic QC -Quality control SC -Subcutaneous SC 50 -Concentration resulting in 50% of the maximum stimulation TLR4 -Toll like receptor 4 TNFα -Tumor necrosis factor α This article has not been copyedited and formatted. The final version may differ from this version.

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Section: Introductionmentioning

confidence: 99%

Pharmacokinetic/Pharmacodynamic Modeling of Dexamethasone Anti-Inflammatory and Immunomodulatory Effects in LPS-Challenged Rats: A Model for Cytokine Release Syndrome

Świerczek

Jusko

2023

The Journal of Pharmacology and Experimental Therapeutics

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A Glucocorticoid-Mediated Immunoregulatory Circuit Integrated at Brain Levels: Our Early Studies and a Present View

Besedovsky,

del Rey

2024

Neuroimmunomodulation

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Background It was known since the 1940’s that pharmacological administration of glucocorticoids can inhibit inflammatory and immune processes, and these hormones are still today among the most widely used therapeutic tools to treat diseases with immune components. However, it became clear later that endogenous glucocorticoids can either support or restrain immune processes. Summary Early studies showed that: a) endogenous levels of glucocorticoids can modulate immune cell activity; b) the immune response itself can stimulate the hypothalamus-pituitary-adrenal (HPA) axis to release glucocorticoids to levels that can exert immunoregulatory effects; c) immune products, later identified as cytokines, mediate this effect. On these bases, the existence of a glucocorticoid-mediated immunoregulatory circuit was proposed. It was also shown that increased levels of endogenous glucocorticoids exert protective effects during infections and other diseases with immune components. However, it was found in animal models and in humans that these effects can be blunted in several immune-linked diseases by defects at several levels, for example by glucocorticoid resistance or by adrenal insufficiency. Evidence was later provided that the glucocorticoid-mediated immunoregulatory circuit can also be activated by cytokines produced not only as consequence of immune stimulation but also following psycho/sensorial and physical stimuli. Thus, this circuit can be integrated at brain levels and, besides stimulating the HPA axis, cytokines can also affect synaptic plasticity, most likely via a tripartite synapse, with astrocytes as neuro-immune cells acting as the third component. Key Messages It is now well established that the glucocorticoid-mediated immunoregulatory circuit plays a central role in maintaining health. However, several variables can condition the efficacy of the effect of endogenous glucocorticoids. Furthermore, since cytokines and other immune products have many other neuro-endocrine and metabolic effects, other neuro-endocrine-immune circuits could simultaneously operate or become predominant during different pathologies. The consideration of these aspects might help to implement strategies to eventually decrease therapeutic doses of exogenous glucocorticoids.

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Baicalein exerts beneficial effects in lipopolysaccharide-induced pulmonary inflammation by modulating macrophage polarization and inhibiting pyroptosis

Kou,

Zhang,

Shi

et al. 2024

Hum Exp Toxicol

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The disruption of the immune system by viral attack is a major influencing factor in the lethality of COVID-19. Baicalein is one of the key effective compounds against COVID-19. The molecular mechanisms regarding the anti-inflammatory properties of Baicalein are still unclear. In this study, we established LPS-induced mice to elucidate the role of Baicalein in the treatment of acute lung injury (ALI) and its potential molecular mechanisms. In vivo experiments showed that Baicalein could significantly ameliorate LPS-induced acute lung injury and reduce proteinous edema in lung tissue. In addition, Baicalein inhibited M1 macrophage polarization, promote M2 macrophage polarization, and regulate inflammatory responses. Furthermore, Baicalein could inhibit the expression of protein molecules associated with pyroptosis and mitigate the lung tissue injury. In summary, we revealed the therapeutic effects of Baicalein in acute lung injury, providing the theoretical basis for its clinical application.

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New Insights on Effects of Glucocorticoids in Patients With SARS-CoV-2 Infection

Cited by 5 publications

References 76 publications

Pharmacokinetic/Pharmacodynamic Modeling of Dexamethasone Anti-Inflammatory and Immunomodulatory Effects in LPS-Challenged Rats: A Model for Cytokine Release Syndrome

Pharmacokinetic/Pharmacodynamic Modeling of Dexamethasone Anti-Inflammatory and Immunomodulatory Effects in LPS-Challenged Rats: A Model for Cytokine Release Syndrome

A Glucocorticoid-Mediated Immunoregulatory Circuit Integrated at Brain Levels: Our Early Studies and a Present View

Baicalein exerts beneficial effects in lipopolysaccharide-induced pulmonary inflammation by modulating macrophage polarization and inhibiting pyroptosis

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