Does remote ischaemic conditioning reduce inflammation? A focus on innate immunity and cytokine response

AbstractThe benefits of remote ischaemic conditioning (RIC) have been difficult to translate to humans, when considering traditional outcome measures, such as mortality and heart failure. This paper reviews the recent literature of the anti-inflammatory effects of RIC, with a particular focus on the innate immune response and cytokine inhibition. Given the current COVID-19 pandemic, the inflammatory hypothesis of cardiac protection is an attractive target on which to re-purpose such novel therapies. A PubMed/MEDLINE™ search was performed on July 13th 2020, for the key terms RIC, cytokines, the innate immune system and inflammation. Data suggest that RIC attenuates inflammation in animals by immune conditioning, cytokine inhibition, cell survival and the release of anti-inflammatory exosomes. It is proposed that RIC inhibits cytokine release via a reduction in nuclear factor kappa beta (NF-κB)-mediated NLRP3 inflammasome production. In vivo, RIC attenuates pro-inflammatory cytokine release in myocardial/cerebral infarction and LPS models of endotoxaemia. In the latter group, cytokine inhibition is associated with a profound survival benefit. Further clinical trials should establish whether the benefits of RIC in inflammation can be observed in humans. Moreover, we must consider whether uncomplicated MI and elective surgery are the most suitable clinical conditions in which to test this hypothesis.

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Rationally synthesized coumarin based pyrazolines ameliorate carrageenan induced inflammation through COX-2/pro-inflammatory cytokine inhibition

MedChemComm ◽

10.1039/c8md00457a ◽

2019 ◽

Vol 10 (3) ◽

pp. 421-430 ◽

Cited By ~ 8

Author(s):

Priyanka Chandel ◽

Anoop Kumar ◽

Nishu Singla ◽

Anshul Kumar ◽

Gagandeep Singh ◽

...

Keyword(s):

Inflammatory Cytokine ◽

Cytokine Inhibition ◽

Cox 2 ◽

Anti Inflammatory

In the present work, coumarin based pyrazolines (7a–g) have been synthesized and investigated for their in vitro and in vivo anti-inflammatory potential.

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Identification of an ASC oligomerization inhibitor for the treatment of inflammatory diseases

Cell Death and Disease ◽

10.1038/s41419-021-04420-1 ◽

2021 ◽

Vol 12 (12) ◽

Author(s):

Paula M. Soriano-Teruel ◽

Guillermo García‑Laínez ◽

María Marco-Salvador ◽

Julián Pardo ◽

Maykel Arias ◽

...

Keyword(s):

Innate Immune System ◽

Inflammatory Cell ◽

Inflammatory Diseases ◽

Primary Cultures ◽

Innate Immune ◽

Cytokine Release ◽

Multifactorial Diseases ◽

Molecule Inhibitor

AbstractThe ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain (CARD)) protein is an scaffold component of different inflammasomes, intracellular multiprotein platforms of the innate immune system that are activated in response to pathogens or intracellular damage. The formation of ASC specks, initiated by different inflammasome receptors, promotes the recruitment and activation of procaspase-1, thereby triggering pyroptotic inflammatory cell death and pro-inflammatory cytokine release. Here we describe MM01 as the first-in-class small-molecule inhibitor of ASC that interferes with ASC speck formation. MM01 inhibition of ASC oligomerization prevents activation of procaspase-1 in vitro and inhibits the activation of different ASC-dependent inflammasomes in cell lines and primary cultures. Furthermore, MM01 inhibits inflammation in vivo in a mouse model of inflammasome-induced peritonitis. Overall, we highlight MM01 as a novel broad-spectrum inflammasome inhibitor for the potential treatment of multifactorial diseases involving the dysregulation of multiple inflammasomes.

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Biomimetic Nanoparticles Potentiate the Anti-Inflammatory Properties of Dexamethasone and Reduce the Cytokine Storm Syndrome: An Additional Weapon against COVID-19?

Nanomaterials ◽

10.3390/nano10112301 ◽

2020 ◽

Vol 10 (11) ◽

pp. 2301

Author(s):

Roberto Molinaro ◽

Anna Pasto ◽

Francesca Taraballi ◽

Federica Giordano ◽

Jamil A. Azzi ◽

...

Keyword(s):

Cytokine Storm ◽

Cytokine Release ◽

Cytokine Release Syndrome ◽

Array Analysis ◽

Pathological Conditions ◽

Significant Survival Advantage ◽

Significant Survival ◽

Biomimetic Nanoparticles ◽

Anti Inflammatory

Recent studies on coronavirus infectious disease 2019 (COVID-19) pathophysiology indicated the cytokine release syndrome induced by the virus as the main cause of mortality. Patients with severe COVID-19 infection present a systemic hyper inflammation that can lead to lung and multi-organ injuries. Among the most recent treatments, corticosteroids have been identified to be effective in mitigating these catastrophic effects. Our group has recently developed leukocyte-derived nanovesicles, termed leukosomes, able to target in vivo the inflamed vasculature associated with pathological conditions including cancer, cardiovascular diseases, and sepsis. Herein, to gain insights on the anti-inflammatory properties of leukosomes, we investigated their ability to reduce uncontrolled inflammation in a lethal model of lipopolysaccharide (LPS)-induced endotoxemia, recapitulating the cytokine storm syndrome observed in COVID-19 infection after encapsulating dexamethasone. Treated animals showed a significant survival advantage and an improved immune response resolution, as demonstrated by a cytokine array analysis of pro- and anti-inflammatory cytokines, chemokines, and other immune-relevant markers. Our results showed that leukosomes enhance the therapeutic activity of dexamethasone and better control the inflammatory response compared to the free drug. Such an approach could be useful for the development of personalized therapies in the treatment of hyperinflammation related to infectious diseases, including the ones caused by COVID-19.

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