Anti-inflammatory Effects Of Statins Research Articles

Role of interleukin 6 signaling pathway in the anti-inflammatory effects of statins on coronary artery disease: Evidence from Mendelian randomization analysis

BackgroundStatins are currently widely used in the prevention of coronary artery disease (CAD) primarily for lipid-lowering with a potential anti-inflammatory effect. However, it is not clear if their potential anti-inflammatory effects are mediated through the interleukin 6 (IL-6) signaling pathway. MethodsUsing the Mendelian randomization (MR) approach followed by multivariable MR analyses, we examined the extent to which the effects of statins on CAD might be mediated through the IL-6 signaling pathway. ResultsOur observations showed that HMG-CoA reductase, using LDL levels as a proxy, had a significant effect on upstream IL-6 (βMR = 0.47, P-IVW = 0.01) and nominally significant effects on IL-6RA (βMR = 0.22, P-IVW = 0.047) and APOB (βMR = 0.82, P-IVW = 1.8 × 10–33). While the IL-6 signaling cascade (IL-6RA βMR = −0.06, P-IVW = 3.45 × 10–20 and IL-6 βMR = −0.03, P-IVW = 0.09) and the anti-inflammatory effect of HMG-CoA reductase (βMR = −0.31, P-IVW = 0.01) was found to influence the risk of CAD, the multivariable MR (MVMR) model indicated that the anti-inflammatory effect of HMG-CoA reductase is not likely to be mediated through the IL-6 signaling cascade, including APOB and IL-6RA (MVMRβ = 0.23, P = 0.688). ConclusionsOur findings suggest that statins may use inflammatory mechanisms independent of the IL-6 signaling pathway to prevent CAD. This result could potentially affect the definition of the target population for statin use.

EXPRESS: Effectiveness of HMG-CoA reductase inhibitors on inflammation and metabolic markers in the US-Mexico border Hispanic population.

HMG-CoA reductase inhibitors (statins) are commonly used for dyslipidemia management to reduce the risk of cardiovascular disease (CVD). High-sensitivity C-reactive protein (hs-CRP) is an emerging systematic low-grade inflammatory marker associated with atherosclerotic CVD development. Despite racial/ethnic disparities in the use and response of statins and the anti-inflammatory effects of statins, the effectiveness of statins on inflammation and metabolic markers is unknown among Hispanics. We performed a retrospective cohort study using 150 adult patients scheduled for an annual physical exam at a family medicine clinic between January 1, 2021, and December 31, 2021. Effect size with a 95% confidence interval (CI) was estimated using adjusted regression analyses. Among 150 patients, 52 (34.67%) received statins. Patients who received statins had significantly reduced median hs-CRP (1.9 vs. 3.2, p=0.007), mean low-density lipoprotein (LDL-C) (101.18 vs. 124.6, p<0.001), and total cholesterol (172.6 vs. 194.5, p<0.001) concentrations compared to those who did not receive statins. In the propensity-scores matched analysis, lower concentrations of log-transformed hs-CRP (regression coefficient [RC], -0.48; 95%CI: -0.89, -0.07), LDL-C (RC, -19.57; 95%CI: -33.04, -6.1), and total cholesterol (RC, -23.47; 95%CI: -38.96, -7.98) were associated with statin use. In addition, hepatic steatosis (adjusted relative risk [aRR]=0.25; 95%CI: 0.08, 0.78, p= 0.017) was significantly lower among patients with the use of statins. Our study suggests that HMG-CoA reductase inhibitors may help reduce inflammation among Hispanic patients with dyslipidemia and hypertension. These findings have useful implications for preventing risk and disparities associated with cardiovascular and other inflammatory-induced diseases among the fastest-growing US Hispanic minorities.

Association between antihyperlipidemic agents and the risk of chronic periodontitis in patients with hyperlipidemia: A population-based retrospective cohort study in Taiwan.

The lipid-lowering and anti-inflammatory effects of statins and fibrates may ameliorate periodontitis. Patients with hyperlipidemia tend to have a worse periodontal status. This study assessed the association between the use of statins/fibrates and the incidence of chronic periodontitis in patients with hyperlipidemia in Taiwan. This retrospective cohort study enrolled patients newly diagnosed with hyperlipidemia between 2001 and 2012 from the 2000 Longitudinal Generation Tracking Database and followed them for 5 years. The study population was divided into four groups: statin monotherapy, fibrate monotherapy, combination therapy (both statins and fibrates), and control (neither statins nor fibrates). Each patient in the treatment group was matched at a ratio of 1:1 with a control. Chronic periodontitis risk was compared in the three study arms by using a Cox proportional hazard model. Chronic periodontitis risk was reduced by 25.7% in the combination therapy group compared with the control group (adjusted hazard ratio [aHR], 0.743; 95% confidence interval (CI), 0.678-0.815). Low dose (<360 cumulative defined daily dose [cDDD]) and shorter duration (<2 years) of statin monotherapy seem to be associated with an increased risk of chronic periodontitis; high dose (≥720 cDDD/≥1080 cDDD) and longer duration (≥3 years) of statin/fibrate monotherapy may be correlated with a lower risk of periodontitis. Hydrophobic statin users had a lower chronic periodontitis risk than hydrophilic statin users. Chronic periodontitis risk was lower in patients with hyperlipidemia on combination treatment with statins and fibrates, and the risk decreased when patients used statins or fibrates for >3 years.

Statins: Beneficial Effects in Treatment of COVID-19.

The recent viral disease COVID-19 has attracted much attention. The disease is caused by SARS-CoV-19 virus which has different variants and mutations. The mortality rate of SARS-CoV-19 is high and efforts to establish proper therapeutic solutions are still ongoing. Inflammation plays a substantial part in the pathogenesis of this disease causing mainly lung tissue destruction and eventually death. Therefore, anti-inflammatory drugs or treatments that can inhibit inflammation are important options. Various inflammatory pathways such as nuclear factor Kappa B (NF-κB), signal transducer of activators of transcription (STAT), nod-like receptor family protein 3 (NLRP), toll-like receptors (TLRs), mitogen-activated protein kinase (MAPK), and mammalian target of rapamycin (mTOR) pathways and mediators, such as interleukin (IL)-6, IL-1β, tumor necrosis factor-α (TNF-α), and interferon-γ (INF-γ), cause cell apoptosis, reduce respiratory capacity and oxygen supply, eventually inducing respiratory system failure and death. Statins are well known for controlling hypercholesterolemia and may serve to treat COVID-19 due to their pleiotropic effects among which are anti-inflammatory in nature. In this chapter, the anti-inflammatory effects of statins and their possible beneficial effects in COVID-19 treatment are discussed. Data were collected from experimental and clinical studies in English (1998-October 2022) from Google Scholar, PubMed, Scopus, and the Cochrane Library.

Statins versus Nonstatin Use in Patients with Chronic Subdural Hematomas Treated with Middle Meningeal Artery Embolization Alone – A Single-Center Experience

Statins have been reported to reduce the rates of recurrence and improve the resolution of chronic subdural hematomas (cSDHs) treated surgically or conservatively. No studies have investigated the effect of statins in patients treated with middle meningeal artery embolization. We performed a retrospective search of our cSDH database to identify patients treated with middle meningeal artery embolization alone. Only patients with at least 1 noncontrast computed tomography scan obtained 3-12weeks after embolization were included. Hematoma volumes were measured at baseline and last noncontrast computed tomography available. The volumes, volume reduction, speed of resolution, and recurrence were compared between patients already receiving statin therapy when admitted and those who were not. Forty-six patients with 50 cSDHs were included (statins, 17 patients with 18 cSDHs vs. nonstatins, 29 patients with 32 cSDHs). The statin group had a significantly higher rate of hyperlipidemia (statin, 64.7% vs. nonstatin, 31%, P= 0.03) but similar demographics, remaining comorbidities, medications, and hematoma thickness, axial and coronal lengths, and baseline volumes. The time between procedure and last noncontrast computed tomography scan was similar between groups. There were no differences between the groups regarding volume reduction, final volume, speed of resolution, complete resolution, and recurrence. Patients treated with middle meningeal artery embolization alone who were on statin therapy had no differences in cSDH resolution or recurrence compared to those who were not on statin therapy. It is possible that the anti-inflammatory effects of statins may not be relevant when supply to the dura is interrupted by treatment with embolization.

Statins and Inflammation.

Chronic inflammation has been recognized as one of the most important pathophysiological mechanisms' initiation and progression of atherosclerosis. Statins belong to most successful therapeutic agents in the prevention and treatment of atherothrombotic vascular disease. Their non-lipid related effects including suppression of inflammation have been repeatedly proven in both experimental and clinical settings. Recently, the importance of inflammation in the process of atherosclerosis has been confirmed by interventions targeting inflammation selectively. Clinical trial with selective inhibitor of a principal inflammatory mediator interleukin 1-beta - canakinumab - confirmed the notion of direct vasculoprotective effects of primarily targeting inflammation. This has increased interest in the non-lipid, pleiotropic and, particularly, anti-inflammatory effects of statins. Anti-inflammatory effects of statins have been proven both experimentally and in clinical settings beyond any doubt. They comprise a direct positive effect on not only many cell types and pathways that are lipid independent but, also, some that are mediated by lipid modification. Undoubtedly, suppression of inflammatory response by statins contributes to their generally positive action in atherosclerosis and represents an important part of the vasculo- and atheroprotective effect of this drug class.

Prolonged use of statins and peripheral neuropathy: A systematic review

Peripheral neuropathy is one of the most common neurological disorder. Traditionally, diabetes mellitus is the most common aetiology of peripheral neuropathy. However, there are many other aetiologies of peripheral neuropathy, such as drug-induced, spinal trauma, alcoholism, vitamin B12 deficiency, and many more. In previous studies, long-term statin use was also associated with peripheral neuropathy. We conducted a systematic search through PubMed and Embase using the protocol following the PRISMA statement in making a systematic review. W e included article that published in the last 10 years (from 2011 until July 2020). Two reviewers extracted data from the articles that have been selected. We extracted the study population, study design, type of intervention, control variable, p-value, and the outcome of the study We found 250 journals in our search strategy, and at the end, 4 journals included. Some studies revealed that peripheral neuropathy was observed during the long-term treatment of statin. However, some studies also revealed that statin does not increase the risk of peripheral neuropathy. The possible mechanism of statin-induced peripheral neuropathy in humans are disturbing the function and integrity of cell membrane, the role of alfa-tocopherol or Vitamin E, and the role of ubiquinone (Coenzyme Q10). In contrast, it is believed that statins lowering the risk of peripheral neuropathy through the anti-inflammatory effects of statins. Different result from each study can be caused by various factors. Besides the peripheral neuropathy side effect that described in the literature, statins are well tolerated. Awareness the side effects would lead to better treatment. Future study about association between statins and peripheral neuropathy is needed.

Anti-inflammatory Effects of Statins in Lung Vascular Pathology: From Basic Science to Clinical Trials.

HMG-CoA reductase inhibitors (or statins) are cholesterol-lowering drugs and are among the most widely prescribed medications in the United States. Statins exhibit pleiotropic effects that extend beyond cholesterol reduction including anti-atherosclerotic, antiproliferative, anti-inflammatory, and antithrombotic effects. Over the last 20years, statins have been studied and examined in pulmonary vascular disorders, including both chronic pulmonary vascular disease such as pulmonary hypertension, and acute pulmonary vascular endothelial injury such as acute lung injury. In both research and clinical settings, statins have demonstrated promising vascular protection through modulation of the endothelium, attenuation of vascular leak, and promotion of endothelial repair following lung inflammation. This chapter provides a summary of the rapidly changing literature, summarizes the anti-inflammatory mechanism of statins on pulmonary vascular disorders, and explores clinical evidence for statins as a potential therapeutic approach to modulation of the endothelium as well as a means to broaden our understanding of pulmonary vasculopathy pathophysiology.

S0773 Association of Statins and NSAIDS With Flare of Inflammatory Bowel Diseases (IBD)

INTRODUCTION: In animal models, statins (Hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors) have been shown to inhibit pro-inflammatory gene expression by blocking Nf-kB (Nuclear Factor kappa-light-chain-enhancer) signaling. Effect of statin on flare of Inflammatory bowel disease (IBD) has not been well studied. Statins also have antifibrotic activity which is unrelated to the anti-inflammatory effect of the drug. Previous studies on impact of Nonsteroidal anti-inflammatory drugs (NSAIDS) on IBD have shown increased as well as decreased flares. We aimed to look at whether use of statins and NSAIDS was associated with reduced rate of flares in patients of IBD, Ulcerative Colitis (UC) and Crohn’s Disease (CD). METHODS: We performed a retrospective cohort study on all patients in our IBD database after obtaining approval from Institutional review board (IRB). IBD patients exposed to statin and NSAIDS were compared to unexposed patients. Outcome was evaluated using Chi-square (X2) analysis. P < 0.05 was considered significant. RESULTS: Our study included 2978 patients. Of these, 1595 had UC, 1367 had CD and rest had IC (Indeterminate colitis). Six hundred sixty-eight patients had statin use and 2310 had no statin use. Statin use was associated with increased flare of IBD in general as well as strongly associated with UC flare (P = .042 and .005 respectively). There was no association between statin exposure and CD flare (P = .984). Exposure to NSAIDS was not associated with increased or decreased frequency of flares in IBD, including UC, CD, and IC (Table 1). CONCLUSION: Our observational analysis showed that statin use is associated with decreased flares of UC but not with CD. Anti-inflammatory effect of statin could be effective in reducing the inflammation seen in mucosa in UC. In CD, antifibrotic effect of the statins may help in prevention of transmural involvement of the gastrointestinal tract and reduce complications, including flares. NSAIDS exposure was not associated with flare of CD. Prospective and randomized control trial studies on effect of statins and NSAIDS on IBD are necessary in future.Table 1.: showing statin and NSAID exposure with IBD flares

A study of effect of low dose atorvastatin therapy on high sensitivity C-reactive protein in patients with modifiable and non-modifiable cardiovascular risk factors in central India

Background: Anti-inflammatory effects of statins have generated maximum interest, as has been demonstrated in a number of studies showing rapid decrease in CRP levels in patients of acute coronary syndromes. This CRP lowering property of statins has also translated into clinical benefits as suggested by reduction in rate of recurrent angina, recurrent myocardial infarction, and mortality.Methods: This prospective, open, and controlled study was conducted on 160 indoor and outdoor patients, for total duration of two years (2005-2006), in GMC Bhopal, MP, India.Results: In all the four groups, baseline serum hs-CRP was statistically significant (p value &lt;0.01) higher than normal hs-CRP level. Mean reduction (%) in hs-CRP after 3 months of statin therapy was 83.6% in group A and 62.4% in group C which is highly significant (p value &lt;0.001). In group B also, 26% hs-CRP reduction was noticed which is statistically significant (p value &lt;0.01). Baseline hs-CRP was statistically significant high (p value &lt;0.01) in hypertensive patients. Percentages reduction in group A (87%) and group C (66%) was statistically significant (p value &lt;0.01). Baseline hs-CRP was statistically significant higher (p value &lt;0.01) than normal population. After 3 months of statin therapy percentage reduction in group A and group C was statistically significant (p value &lt;0.01). Conclusions: Low dose atorvastatin can significantly reduce CRP level in patients with risk factors for cardiovascular disease. Early initiation of low dose atorvastatin can reduce this inflammatory marker in both ACS and high risk for ACS patients and can prevent major adverse cardiac events.

Statins versus placebo for people with chronic obstructive pulmonary disease

Statins versus placebo for people with chronic obstructive pulmonary disease

Effects of simvastatin on matrix metalloproteinase regulation in IL-1β-induced SW1353 cells

The present study shows the basis for the anti-inflammatory effects of statins in interleukin 1β (IL-1β) induced SW1353 chondrosarcoma cell-line. The cells were pre-treated with simvastatin (5 μM, 10 μM, and 50 μM), followed by IL-1β (5 ng/mL) stimulation. Effects of simvastatin on cell viability and cytotoxicity of chondrocytes were measured with WST-1 and lactate dehydrogenase (LDH) assays, respectively. Under inflammatory conditions, in the absence/presence of simvastatin, the changes in matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase-1 (TIMP-1) expression levels were examined. Expression levels of MMP-1, -2, -3, -9, -13, and TIMP-1 and -2 were examined by qPCR. MMP-1, -9, -13, TIMP-1, and -2 levels were also determined by Western blotting. Gelatin zymography was performed to analyze the released and intracellular MMP-2 and MMP-9 activity levels. The results showed that simvastatin downregulated the degradation related genes MMP-3, MMP-13, MMP-2, MMP-9 and TIMP-2 in a dose-dependent manner.

Anti-inflammatory effect of statin in coronary aneurysms late after Kawasaki disease

Anti-inflammatory effect of statin in coronary aneurysms late after Kawasaki disease

Statins impact primary embryonic mouse neural stem cell survival, cell death, and fate through distinct mechanisms.

Statins inhibit HMG-CoA reductase, the rate-limiting enzyme in the cholesterol biosynthesis pathway (CBP), and are used for the prevention of cardiovascular disease. The anti-inflammatory effects of statins may also provide therapeutic benefits and have led to their use in clinical trials for preeclampsia, a pregnancy-associated inflammatory condition, despite their current classification as category X (i.e. contraindicated during pregnancy). In the developing neocortex, products of the CBP play essential roles in proliferation and differentiation of neural stem-progenitor cells (NSPCs). To understand how statins could impact the developing brain, we studied effects of pravastatin and simvastatin on primary embryonic NSPC survival, proliferation, global transcription, and cell fate in vitro. We found that statins dose dependently decrease NSPC expansion by promoting cell death and autophagy of NSPCs progressing through the G1 phase of the cell cycle. Genome-wide transcriptome analysis demonstrates an increase in expression of CBP genes following pravastatin treatment, through activation of the SREBP2 transcription factor. Co-treatment with farnesyl pyrophosphate (FPP), a CBP metabolite downstream of HMG-CoA reductase, reduces SREBP2 activation and pravastatin-induced PARP cleavage. Finally, pravastatin and simvastatin differentially alter NSPC cell fate and mRNA expression during differentiation, through a non-CBP dependent pathway.

Are the effects of drugs to prevent and to treat heart failure always concordant? The statin paradox and its implications for understanding the actions of antidiabetic medications

Most treatments for chronic heart failure are effective both in preventing its onset and reducing its progression. However, statins prevent the development of heart failure, but they do not decrease morbidity and mortality in those with established heart failure. This apparent discordance cannot be explained by an effect to prevent interval myocardial infarctions. Instead, it seems that the disease that statins were preventing in trials of patients with a metabolic disorder was different from the disease that they were treating in trials of chronic heart failure. The most common phenotype of heart failure in patients with obesity and diabetes is heart failure with a preserved ejection fraction (HFpEF). In this disorder, the anti-inflammatory effects of statins might ameliorate myocardial fibrosis and cardiac filling abnormalities, but these actions may have little relevance to patients with heart failure and a reduced ejection fraction (HFrEF), whose primary derangement is cardiomyocyte loss and stretch. These distinctions may explain why statins were ineffective in trials that focused on HFrEF, but have been reported to produce favourable effects in observational studies of HFpEF. Similarly, selective cytokine antagonists were ineffective in HFrEF, but have been associated with benefits in HFpEF. These observations may have important implications for our understanding of the effects of antihyperglycaemic medications. Glucagon-like peptide-1 receptor agonists have had neutral effects on heart failure events in people at risk for HFpEF, but have exerted deleterious actions in HFrEF. Similarly, sodium-glucose co-transporter 2 inhibitors, which exert anti-inflammatory effects and reduce heart failure events in patients who are prone to HFpEF, may not be effective in HFrEF. The distinctions between HFrEF and HFpEF may explain why the effects of drugs on heart failure events in diabetes trials may not be relevant to their use in patients with systolic dysfunction.

Statins as a preventative therapy for venous thromboembolism.

The anti-inflammatory effects of statins have likely not been used to their fullest extent, particularly in reducing venous thromboembolic events. Current therapy for thrombotic events hinges on anticoagulation via heparin, warfarin or new oral anticoagulants. Interventional procedures with thrombectomy may also play a critical role. Unfortunately, thrombotic events can occur and recur despite meticulous anticoagulation therapy. Venous thromboembolism (VTE) includes both deep vein thrombosis (DVT) and pulmonary embolism (PE), two complicated and prevalent diseases that can cause chronic disease states such as post-thrombotic syndrome (PTS). In 2009 the JUPITER trial demonstrated that rosuvastatin may be effective when dealing with vascular inflammation by providing an anti-inflammatory effect. Multiple subsequent studies have looked at this association with some promising findings. The mechanism of action for statins is not entirely understood but there has been a variety of proposals and subsequent testing of inflammatory biomarkers. Additional prospective trials are needed to confirm the possible benefit of VTE reduction through an anti-inflammatory effect, but if this can be shown then statins may become a safe adjunctive therapy for VTE prevention.

The Anti-Inflammatory Effects of Statins on Coronary Artery Disease: An Updated Review of the Literature.

Background:Statins have long been used for the protection against coronary artery disease (CAD). Their beneficial effect apart from cholesterol reduction lies in their pleiotropic properties. Emerging evidence from laboratory studies and clinical trials as well have pointed out the pivotal role of inflammation on the initiation and exacerbation of atherosclerosis; a major cause of CAD. Inflam-mation markers such as high sensitivity C-reactive protein and adhesion molecules are shown to in-crease in CAD patients and are used as prognostic tools. It is well known that statins can actually re-duce the circulating levels of these agents slowing therefore the inflammatory process; interestingly not all types have the same outcome.Conclusion:The anti-inflammatory effect of statins on the formation of atherosclerotic plaque and the function of endothelial cells is thus of particular importance as these agents can actually ameliorate CAD prognosis

97 Can pre-operative troponin levels predict post-operative mortality following non-cardiac surgery?

IntroductionDespite advances in surgical and anaesthetic techniques, non-cardiac surgery still has a significant mortality. We hypothesised that pre-operative troponin levels might predict post-operative mortality.MethodsPatients undergoing elective and urgent/emergency non-cardiac surgery...

Single intra-articular injection of fluvastatin-PLGA microspheres reduces cartilage degradation in rabbits with experimental osteoarthritis.

Statins are cholesterol-lowering drugs that inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, a rate-limiting enzyme of the mevalonate pathway. The anti-inflammatory effect of statins has been reported in recent years. The present study investigated therapeutic effects of the local administration of statin in osteoarthritis (OA). We assessed clinically used statins and selected fluvastatin for further experimentation, as it showed potent anabolic and anti-catabolic effects on human OA chondrocytes. To achieve controlled intra-articular administration of statin, we developed an intra-articular injectable statin using poly(lactic-co-glycolic acid) (PLGA) as a drug delivery system (DDS). The release profile of the statin was evaluated in vitro. Finally, therapeutic effects of fluvastatin-loaded PLGA microspheres (FLU-PLGA) were tested in a rabbit OA model. Rabbit knees were divided into four subgroups: group 1-A, PLGA-treated group; group 1-B, PLGA contralateral saline control group; group 2-A, FLU-PLGA-treated group; and group 2-B, FLU-PLGA contralateral saline control group. Histological analysis 5 weeks after intra-articular injection revealed that OARSI scores were lower in group 2-A. No significant differences in OARSI scores were observed between groups 1-A, 1-B, and 2-B. This study indicates that a single intra-articular injection of fluvastatin-loaded PLGA microspheres could be a novel therapeutic approach for treating patients with OA. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2465-2475, 2017.

Statins Reduce Lipopolysaccharide-Induced Cytokine and Inflammatory Mediator Release in an In Vitro Model of Microglial-Like Cells.

The anti-inflammatory effects of statins (HMG-CoA reductase inhibitors) within the cardiovascular system are well-established; however, their neuroinflammatory potential is unclear. It is currently unknown whether statins' neurological effects are lipid-dependent or due to pleiotropic mechanisms. Therefore, the assumption that all statin compounds will have the same effect within the central nervous system is potentially inappropriate, with no studies to date having compared all statins in a single model. Thus, the aim of this study was to compare the effects of the six statins (atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin) within a single in vitro model of neuroinflammation. To achieve this, PMA-differentiated THP-1 cells were used as surrogate microglial cells, and LPS was used to induce inflammatory conditions. Here, we show that pretreatment with all statins was able to significantly reduce LPS-induced interleukin (IL)-1β and tumour necrosis factor (TNF)-α release, as well as decrease LPS-induced prostaglandin E2 (PGE2). Similarly, global reactive oxygen species (ROS) and nitric oxide (NO) production were decreased following pretreatment with all statins. Based on these findings, it is suggested that more complex cellular models should be considered to further compare individual statin compounds, including translation into in vivo models of acute and/or chronic neuroinflammation.