Rosuvastatin Is Effective to Decrease CD8 T-Cell Activation Only in HIV-Infected Patients With High Residual T-Cell Activation Under Antiretroviral Therapy

Weiss, Laurence; Chevalier, Mathieu F.; Assoumou, Lambert; Paul, Jean–Louis; Alhenc‐Gelas, Martine; Didier, Céline; Taïbi, Saïd; Manea, Elena-Maria; Campa, Pauline; Girard, Pierre‐Marie; Costagliola, Dominique

doi:10.1097/qai.0000000000000879

Cited by 11 publications

(7 citation statements)

References 40 publications

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“…uncertain generalizability. In this context, different statins have been reported to reduce serum proinflammatory cytokines (e.g., TNF-α, IL-6, IL-8), C-reactive protein (CRP), and T cell and monocyte activation (8,11,13), some of these effects within 6-8 weeks (8,14) or earlier (9) and in a manner independent of serum cholesterol reduction (15). There is a great deal of heterogeneity across these clinical reports, however, including some that failed to observe any immune effects (10,12,16).…”

Section: L I N I C a L M E D I C I N Ementioning

confidence: 99%

“…Most studies on the immune effects of statins, however, have been performed either in rodent models, commonly using very high doses delivered parenterally (3,4), or in in vitro cell-based studies, using supraphysiologic concentrations (5)(6)(7). Reported effects of statins on the human immune system in vivo have largely derived from studies of patients with hypercholesterolemia, coronary artery disease, and/or HIV infection (8)(9)(10)(11)(12) and are thus of insight.jci.org https://doi.org/10.1172/jci.insight.131530…”

Section: Introductionmentioning

confidence: 99%

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Effects of rosuvastatin on the immune system in healthy volunteers with normal serum cholesterol

Karmaus¹,

Shi²,

Biancotto³

et al. 2019

JCI Insight

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5 The CHI Consortium is detailed in the supplemental material. BACKGROUND. HMG-CoA reductase inhibitors (statins) are prescribed to millions of people. Statins are antiinflammatory independent of their cholesterol-reducing effects. To date, most reports on the immune effects of statins have assayed a narrow array of variables and have focused on cell lines, rodent models, or patient cohorts. We sought to define the effect of rosuvastatin on the "immunome" of healthy, normocholesterolemic subjects. METHODS.We conducted a prospective study of rosuvastatin (20 mg/d × 28 days) in 18 statin-naive adults with LDL cholesterol <130 mg/dL. A panel of >180 immune/biochemical/endocrinologic variables was measured at baseline and on days 14, 28, and 42 (14 days after drug withdrawal). Drug effect was evaluated using linear mixed-effects models. Potential interactions between drug and baseline high-sensitivity C-reactive protein (hsCRP) were evaluated. RESULTS.A wide array of immune measures changed (nominal P < 0.05) during rosuvastatin treatment, although the changes were modest in magnitude, and few met an FDR of 0.05. Among changes noted were a concordant increase in proinflammatory cytokines (IFN-γ, IL-1β, IL-5, IL-6, and TNF-α) and peripheral blood neutrophil frequency, and a decline in activated Treg frequency. Several drug effects were significantly modified by baseline hsCRP, and some did not resolve after drug withdrawal. Among other unexpected rosuvastatin effects were changes in erythrocyte indices, glucose-regulatory hormones, CD8 + T cells, and haptoglobin. CONCLUSION.Rosuvastatin induces modest changes in immunologic and metabolic measures in normocholesterolemic subjects, with several effects dependent on baseline CRP. Future, larger studies are warranted to validate these changes and their physiological significance. TRIAL REGISTRATION. ClinicalTrials.gov NCT01200836.

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Section: L I N I C a L M E D I C I N Ementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of rosuvastatin on the immune system in healthy volunteers with normal serum cholesterol

Karmaus¹,

Shi²,

Biancotto³

et al. 2019

JCI Insight

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“…No significant variations in the plasma levels of hsCRP, IL-6, CD14, and D-dimers between baseline and week 12 were reported. 22 In our observational analysis, a 12-month treatment with rosuvastatin at 10 mg daily was effective to significantly reduce plasma levels of D-dimer and of two inflammatory markers (IL-8 and IL-12) in 54 HIV-infected patients under suppressive cART. This is the second study investigating the effect of statins on the D-dimer among HIV-positive persons, after the study by Weiss et al 22 but is the first study showing a significant decrease in the D-dimer level associated with statin therapy in HIV-positive people.…”

Section: Rosuvastatin Coagulation and Inflammationmentioning

confidence: 78%

Significant Decrease in Plasma Levels of D-Dimer, Interleukin-8, and Interleukin-12 After a 12-Month Treatment with Rosuvastatin in HIV-Infected Patients Under Antiretroviral Therapy

Calza

Colangeli

Magistrelli

et al. 2017

AIDS Research and Human Retroviruses

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“…Fluvastatin-pretreated donor cells attenuated CTL function in acute graft-versus-host disease mouse model (37). Rosuvastatin suppressed CTL activity in some subpopulations of healthy subjects (38) and HIV-infected patients (39). Direct antiviral effect-inhibition or slowing down viral replication is common to several statins, due to their ability of inhibiting cholesterol production, reducing the availability of some isoprenoids that are essential for regulating the virus life cycle and by inhibiting the activity of regulatory proteins related to virus intracellular life cycle (40).…”

Section: Statins: Tregs Induction-simvastatin and Lovastatin Inducedmentioning

confidence: 98%

The Binary Model of Chronic Diseases Applied to COVID-19

Elkoshi

2021

Front. Immunol.

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A binary model for the classification of chronic diseases has formerly been proposed. The model classifies chronic diseases as “high Treg” or “low Treg” diseases according to the extent of regulatory T cells (Treg) activity (frequency or function) observed. The present paper applies this model to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The model correctly predicts the efficacy or inefficacy of several immune-modulating drugs in the treatment of severe coronavirus disease 2019 (COVID-19) disease. It also correctly predicts the class of pathogens mostly associated with SARS-CoV-2 infection. The clinical implications are the following: (a) any search for new immune-modulating drugs for the treatment of COVID-19 should exclude candidates that do not induce “high Treg” immune reaction or those that do not spare CD8+ T cells; (b) immune-modulating drugs, which are effective against SARS-CoV-2, may not be effective against any variant of the virus that does not induce “low Treg” reaction; (c) any immune-modulating drug, which is effective in treating COVID-19, will also alleviate most coinfections; and (d) severe COVID-19 patients should avoid contact with carriers of “low Treg” pathogens.

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Rosuvastatin Is Effective to Decrease CD8 T-Cell Activation Only in HIV-Infected Patients With High Residual T-Cell Activation Under Antiretroviral Therapy

Abstract: This study shows that combining rosuvastatin with effective ART can result in a sustained decrease in CD8 T-cell activation and highlights the importance of identifying patients who can benefit from specific immunotherapeutic strategies.

Cited by 11 publications

References 40 publications

Effects of rosuvastatin on the immune system in healthy volunteers with normal serum cholesterol

Effects of rosuvastatin on the immune system in healthy volunteers with normal serum cholesterol

Significant Decrease in Plasma Levels of D-Dimer, Interleukin-8, and Interleukin-12 After a 12-Month Treatment with Rosuvastatin in HIV-Infected Patients Under Antiretroviral Therapy

The Binary Model of Chronic Diseases Applied to COVID-19

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