Atorvastatin suppresses interferon-<i>γ</i>-induced neopterin formation and tryptophan degradation in human peripheral blood mononuclear cells and in monocytic cell lines

Neurauter, Gabriele; Wirleitner, Barbara; Laich, Andreas; Schennach, Harald; Weiss, Günter; Fuchs, Dietmar

doi:10.1046/j.1365-2249.2003.02021.x

Cited by 78 publications

(67 citation statements)

References 27 publications

(40 reference statements)

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“…High quality of red wine, e.g. barrique (2), exogenously added immunomodulating Compounds appeared to have superior cardioprotective effects, but (7,8). Neopterin, a metabolite of guanosine triphoson the other band not only red wine, but also other phate, is produced in humans and primates by monoalcoholic beverages reduce cardiovascular risk (3).…”

Section: Introductionmentioning

confidence: 99%

Wine and Grape Juice Modulate Interferon-y-induced Neopterin Production and Tryptophan Degradation in Human PBMC

et al. 2004

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Population-based studies suggest moderate and regulär consumption of alcoholic beverages and especially of red wine to reduce morbidity and mortality from coronary heart disease. These beverages may interfere with immune acüvation cascades crucial in the pathogenesis of coronary heart diseases. Neopterin concentrations in human body tluids were found to increase in the course of coronary heart disease indicating the activity of the atherogenetic process. In this study, human peripheral blood mononuclear cells (PBMC) stimulated with mitogens phytohaemagglutinin and concanavalin A were exposed to red and white wines, to ethanol and to grape juice as a non-alcoholic control in vitro. Neopterin production and tryptophan dcgradation were mcasured in supcrnalants. Both biochemical effects are induced by Thl-type cytokine interferon-y and allow monitoring of immune actnation. In stimulated PBMC increased production of neopterin and degradation of tryptophan was observcd Red and white wines, as well as grape juice mhibited these stimulation-induced effects, higher concentrations being more cffective. Ethanol had comparably small if any effect, Red and white wines as well as grape juice do\\ nregulate cytokine-mediated effects in PBMC. Most likely, antioxidant ingredients of wine and grape juicc such as resveratrol are capable of interfering with immunologic pathways which appear to be of relevance, e g.. in the pathogenesis of cardiovascular disease.

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Section: Introductionmentioning

confidence: 99%

Wine and Grape Juice Modulate Interferon-y-induced Neopterin Production and Tryptophan Degradation in Human PBMC

et al. 2004

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“…Neopterin production and tryptophan degradation were monitored in cytokine-treated mononuclear cells after treatment with atorvastatin. The investigators found that atorvastatin at high doses (100 μM) inhibited neopterin formation and tryptophan degradation completely but that low doses (10 μM) of that drug were only partially effective (17). That finding is important because statins were shown to suppress the cellular immune system.…”

Section: Discussionmentioning

confidence: 86%

“…Neurauter et al (17) conducted in-vitro investigations on the effects of atorvastatin on the T-cell-macrophage system in peripheral blood mononuclear cells and in human monocytic cell lines. Neopterin production and tryptophan degradation were monitored in cytokine-treated mononuclear cells after treatment with atorvastatin.…”

Section: Discussionmentioning

confidence: 99%

Pravastatin therapy fails to suppress post-PCI inflammatory response measured by serum neopterin and CRP levels

Bozbaş¹,

Mermer²,

Yildirir³

et al. 2011

Anadolu Kardiyol Derg

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ÖZETAmaç: Perkütan koroner girişim (PKG) sonrası hem lokal, hem de sistemik bir enflamatuvar yanıt meydana gelmektedir. Statinler lipit düşürücü etkilerinin yanında iyi tanımlanmış antienflamatuvar etkilere de sahiptirler. Bu çalışmada pravastatin tedavisinin elektif PKG yapılan hastalarda işlem sonrası serum C-reaktif protein (CRP) ve neopterin düzeyine olan etkisinin değerlendirilmesi amaçlanmıştır. Yöntemler: Bu prospektif, randomize çalışmaya elektif PKG planlanan 93 hasta dahil edildi. Grup 1'e (n=30) pravastatin 10mg/gün, Grup 2'ye (n=29) 40 mg/gün başlandı; Grup 3 (n=34) kontrol grubu alındı ve bu gruba lipit düşürücü tedavi verilmedi. Hastalardan işlem öncesi, işlemden sonra kan örnekleri alınarak serum CRP ve neopterin düzeyleri çalışıldı. Devamlı değişkenlerin gruplar arası karşılaştırılması ANOVA ve KruskalWallis testi ile yapıldı. Devamlı olmayan değişkenler ise Ki-kare testi ile değerlendirildi. Bulgular: Hastaların demografik özellikleri ve PKG ile ilişkili verileri (işlem yapılan damar sayısı, balon şişirme sayısı ve süresi) gruplar arasında benzer idi (p>0.05). Serum CRP ve neopterin düzeylerinde işlemden sonra anlamlı artış saptandı (p<0.001). İşlem öncesi ve sonrası ortalama serum neopterin düzeyleri gruplar arasında şu şekilde idi: Grup 1: 13.3±5.9 ve 22.8±15.4 nmol/L; Grup 2: 16.9±10.2 ve 22.0±14.9 nmol/L; kontrol grubu: 15.2±11.9 ve 18.8±11.5nmol/L. İşlem öncesi başlanan pravastatin tedavisinin bu enflamasyon parametrelerine anlamlı bir etkisi saptanmadı (F=0.5, p=0.6). Sonuç: Perkütan koroner girişim (PKG) belirgin bir enflamatuvar yanıta yol açmaktadır. İşlem öncesi 2 farklı dozda başlanan pravastatin tedavisinin kısa süreli izlemde bu inflamatuvar yanıtı baskılamada yetersiz kaldığı görülmüştür. Bu konunun daha iyi aydınlatılabilmesi için ileri çalış-malara ihtiyaç vardır. (Anadolu Kardiyol Derg 2011; 11: 207-12) Anahtar kelimeler: Statin, C-reaktif protein, neopterin, perkütan koroner girişim ABSTRACT Objective: Percutaneous coronary intervention (PCI) is known to induce both local and systemic inflammatory states. In addition to lowering lipid levels, statins exert well-proven anti-inflammatory effects. We investigated the effects of pravastatin on serum C-reactive protein (CRP) and neopterin levels in the short term after elective PCI. Methods: In this randomized prospective study, 93 patients undergoing elective PCI were enrolled. Group 1 (n=30) received pravastatin at a dose of 10 mg/day, Group 2 (n=29) was given 40 mg/day, and Group 3 (n=34) served as the control group and received no lipid-lowering drugs. Blood samples were drawn before and after PCI to measure serum CRP and neopterin levels. Differences among the groups for continuous variables were evaluated by the ANOVA and the Kruskal-Wallis test as appropriate. The Chi-square test was used for comparison of categorical variables. Results: Demographic features and the characteristics of the PCI, including the number of vessels and lesions and the duration and number of inflations, did not differ among groups (p>0.05). Serum CRP...

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“…In addition to lowering cholesterol levels, reduction of inflammation and/or oxidative stress associated with atherosclerosis is one of the potential mechanisms contributing to the beneficial effects of lipid lowering treatment with statins. Statins have been shown to reduce neopterin levels both in vitro and in vivo, confirming their immunomodulatory properties [11,[20][21][22]. On the other hand, in some cases, statin therapy did not affect inflammatory biomarkers and/or neopterin [23].…”

Section: Discussionmentioning

confidence: 99%

“…In addition to their lipid lowering properties, there is clinical evidence that statins exhibit anti-inflammatory action due to the extensive immunomodulatory properties [10]. Furthermore, a statin derivative was found to down-regulate neopterin production and Trp degradation in monocytic cells in vitro [11]. Data regarding the effects of statins on both of immunomodulation markers and folate levels in patients with CVDs are limited.…”

Section: Introductionmentioning

confidence: 99%

Folate, neopterin and kynurenine pathway in patients with statin therapy

et al. 2016

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AbstractStatins, widely used antihyperlipidemic drugs, also have immunomodulatory properties independent from their lipid lowering effect. Even with slight modulations in the immune system, pteridine levels can display changes. The effect of statins on pteridines and related pathways has been demonstrated in a limited number of studies. The aim of the study was to evaluate the possible changes in neopterin and folate levels, and tryptophan (Trp) degradation in hyperlipidemic patients. Patients who were admitted to the cardiology clinic were randomly grouped if they were having statin treatment (n=69) or not (n=36). Serum Trp and kynurenine (Kyn), erythrocyte folate, and urinary neopterin levels were measured. It was found that urinary neopterin levels were significantly higher in patients on statin treatment (p<0.05) while levels of folate, Trp, Kyn, and Kyn-to-Trp ratios (Kyn/Trp) presented no significant changes (all, p>0.05). The correlation of the measured parameters was also evaluated and neopterin, folate and tryptophan degradation were found to be positively correlated. According to the results, neopterin levels, folate status and Trp degradation were altered in patients with statin treatment in comparison with the patients not receiving statin therapy. In order to point out the direct effect of statins on pteridines, further studies presenting both pre- and post-statin treatment of these parameters are needed.

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Atorvastatin suppresses interferon-γ-induced neopterin formation and tryptophan degradation in human peripheral blood mononuclear cells and in monocytic cell lines

Cited by 78 publications

References 27 publications

Wine and Grape Juice Modulate Interferon-y-induced Neopterin Production and Tryptophan Degradation in Human PBMC

Wine and Grape Juice Modulate Interferon-y-induced Neopterin Production and Tryptophan Degradation in Human PBMC

Pravastatin therapy fails to suppress post-PCI inflammatory response measured by serum neopterin and CRP levels

Folate, neopterin and kynurenine pathway in patients with statin therapy

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