Rationale of Statin Therapy in Septic Patients

Piechota, Mariusz; Barylski, Marcin; Hannam, Simon; Piechota-Urbańska, Magdalena; Banach, Maciej

doi:10.2174/1570161111311050018

Cited by 9 publications

(6 citation statements)

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“…The clinical application of this hypothesis is that lipoxins, resolvins, protectins, maresins, nitrolipids and ghrelin and/or their more stable synthetic analogues could prove to be useful in the prevention and management of sepsis. In this context, it is interesting to note that statins that have been shown to be of use in sepsis [61] are known to enhance the synthesis of lipoxins [62, 63]. …”

Section: Discussionmentioning

confidence: 99%

State of the art papers HLA-DR expression, cytokines and bioactive lipids in sepsis

Das¹

2014

aoms

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Sepsis accounts for more than 200,000 deaths annually in the USA alone. Both inflammatory and anti-inflammatory responses occur simultaneously in sepsis, the early phase dominated by the hyperinflammatory response and the late phase by immunosuppression. This late immunosuppression phase leads to loss of the delayed type hypersensitivity response, failure to clear the primary infection and development of secondary infections. Based on the available data, I hypothesize that failure to produce adequate amounts of inflammation resolving lipid mediators may be at the centre of both the hyperinflammatory response and late immunosuppression seen in sepsis. These proresolving lipids – lipoxins, resolvins and protectins – suppress exacerbated activation of leukocytes and macrophages, inhibit excess production of pro-inflammatory cytokines, initiate resolution of inappropriate inflammation, augment clearance of bacteria and other pathogens, and restore homeostasis. If true, this implies that administration of naturally occurring lipoxins, resolvins, protectins, maresins and nitrolipids by themselves or their more stable synthetic analogues such as 15-epi-16-(para-fluorophenoxy)-lipoxin A4-methyl ester, a synthetic analogue of 15-epi-lipoxin A4, and 15(R/S)-methyl-LXA4 may form a new approach in the prevention (in the high-risk subjects), management of sepsis and in resolving the imbalanced inflammatory process such that sepsis is ameliorated early. In addition, recent studies have suggested that nociceptin and cold inducible RNA binding protein (CIRBP) also have a role in the pathobiology of sepsis. It is suggested that both nociceptin and CIRBP inhibit the production of lipoxins, resolvins, protectins, maresins, and nitrolipids and thus play a role in sepsis and septic shock.

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Section: Discussionmentioning

confidence: 99%

State of the art papers HLA-DR expression, cytokines and bioactive lipids in sepsis

Das¹

2014

aoms

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“…However, this study was limited by a short duration of simvastatin administration, which was probably administered too late to see an effect-patients received a statin after several days in the ICU and had dysfunction of at least one organ [46]. Other studies focused on statin therapy to prevent sepsis or against community-acquired infections [37,38,47] supported a role for these drugs in severe infections.…”

Section: Use Of Statins In Human Viral Infectionsmentioning

confidence: 99%

Cholesterol in Relation to COVID-19: Should We Care about It?

Radenković

Chawla

Pirro

et al. 2020

JCM

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130

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Current data suggest that infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing corona virus disease-19 (COVID-19) seems to follow a more severe clinical course in patients with cardiovascular disease (CVD), hypertension, and overweight/obesity. It appears that lipid-lowering pharmacological interventions, in particular statins, might reduce the risk of cardiovascular complications caused by COVID-19 and might potentially have an additional antiviral activity. It has been shown that high cholesterol levels are associated with more lipid rafts, subdomains of the plasma membrane that can harbour angiotensin-converting enzyme 2 (ACE2) receptors for the S-protein of SARS-CoV-2. Evidence of the importance of cholesterol for viral entry into host cells could suggest a role for cholesterol-lowering therapies in reducing viral infectivity. In addition to their lipid-lowering and plaque-stabilisation effects, statins possess pleiotropic effects including anti-inflammatory, immunomodulatory, and antithrombotic activities. Lower rates of mortality and intubation have been reported in studies investigating statin therapy in influenza infection, and statin therapy was shown to increase viral clearance from the blood during chronic hepatitis C infection. Statins may also serve as potential SARS-CoV-2 main protease inhibitors, thereby contributing to the control of viral infection. In this review, we elaborate on the role of cholesterol level in the process of the coronavirus infection and provide a critical appraisal on the potential of statins in reducing the severity, duration, and complications of COVID-19.

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“…Statins and the Covid-19 main protease: in silico evidence on direct interaction Željko Reiner 1 , Mahdi Hatamipour 2,3 , Maciej Banach 4,5 , Matteo Pirro 6 , Khalid Al-Rasadi 7 , Tannaz Jamialahmadi 8,9 , Dina Radenkovic 10 , Fabrizio Montecucco 11,12 , Amirhossein Sahebkar 13,14,15 A b s t r a c t introduction: No proven drug and no immunisation are yet available for COVID-19 disease. The SARS-CoV-2 main protease (Mpro), a key coronavirus enzyme, which is a potential drug target, has been successfully crystallised.…”

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confidence: 99%

“…Key words: COVID-2019, main protease, statins, 6LU7, docking. flammatory, anti-thrombotic, and immunomodulatory functions [8][9][10][11][12][13][14][15]. Furthermore, statin treatment can interfere with viral infectivity through inhibition of glycoprotein processing.…”

mentioning

confidence: 99%