Effect of Statins on Serum Levels of TNF-alpha and Interleukin-6 in Patients with Kidney Disease: A Meta-analysis of Randomized Clinical Trials.

BACKGROUND AND OBJECTIVES: Some clinical trials have indicated the beneficial effects of statins in patients with kidney disease, while others have reported no positive effect of statins in these patients. We conducted this meta-analysis to identify the effects of statins on serum levels of interleukin-6 (IL-6) and Tumor Necrosis Factor Alpha (TNF-α) in patients with kidney disease. DESIGNS AND METHODS: A systematic literature search was performed using PubMed, Scopus, and Web of Science databases to identify all studies published from inception to August, 2022. The major outcome variable was the Weighted Mean Difference (WMD). Eligible studies were stratified based on target population, intervention duration, dosage and type of statins, and solubility of statins. RESULTS: Meta-analysis performed on seven publications (8 studies), including 213 patients with kidney disease and 188 control individuals, indicated that the concentration of IL-6 was marginally decreased in patients with kidney disease following statin therapy disease (WMD = -1.15 pg/mL; 95% CI = -2.33 to 0.04, P = 0.05, 2 =68.5%)). The findings of subgroup analysis based on the dosage of statins showed that neither highintensity nor moderate/low-intensity statin treatment could significantly influence the serum level of IL-6. Lipophilic statins were more effective than hydrophilic statins, and they marginally decreased the levels of IL6 (WMD = -1.21 pg/mL; 95% CI = -2.43 to 0, P = 0.05, I2 = 55.7%)). Meta-analysis of four publications (five studies) with 157 patients with kidney disease and 132 control subjects showed that statins reduced the serum levels of TNF-α in patients with kidney disease when compared with control individuals (WMD= -2.66 pg/mL; 95% CI = -4.26 to -1.06, P < 0.001, I2 = 63%). CONCLUSION: Statins only marginally decreased the concentration of IL-6 in patients with kidney disease, but neither high-intensity nor moderate/low-intensity statin treatment could significantly influence the level of IL6. However, statins reduced serum levels of TNF-α in patients with kidney disease.

Immunoregulatory Effects of the Active Form of Vitamin D (Calcitriol), Individually and in Combination with Curcumin, on Peripheral Blood Mononuclear Cells (PBMCs) of Multiple Sclerosis (MS) Patients.

OBJECTIVES: Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease affecting the central nervous system. Immune cell subsets, notably T helper (Th) 17 and Th1, exert important roles in MS pathogenesis. Whereas, Treg cells modulate the disease process. Calcitriol, the active form of vitamin D, and curcumin, a bioactive compound derived from turmeric, play immunomodulatory effects relevant to autoimmune disorders, including MS. The objective of this study is to investigate the effects of calcitriol and Curcumin on Peripheral blood mononuclear cells (PBMCs) of individuals with MS. METHODS: PBMCs from twenty MS patients were isolated, cultured, and exposed to 0.004 µg/mL of calcitriol and 10 µg/mL of curcumin. The cells underwent treatment with singular or combined doses of these components to assess potential cumulative or synergistic immunomod-ulatory effects. Following treatment, the expression levels of genes and the cellular population of Treg, Th1 and Th17 were evaluated using Real-time PCR and flow cytometry. RESULTS: Treatment with curcumin and calcitriol led to a significant reduction in the expression levels of inflammatory cytokines and transcription factors related to Th1 and Th17 cells, includ-ing IFN-γ, T-bet, IL-17, and RORC. Furthermore, the frequency of these cells decreased follow-ing treatment. Additionally, curcumin and calcitriol treatment resulted in a significant upregu-lation of the FOXP3 gene expression and an increase in the frequency of Treg cells. CONCLUSION: This study demonstrates that curcumin and calcitriol can effectively modulate the inflammatory processes intrinsic to MS by mitigating the expression of inflammatory cytokines by Th1 and Th17 cells while concurrently enhancing the regulatory role of Treg cells. Moreover, the combined treatment of curcumin and calcitriol did not yield superior outcomes compared to single-dosing strategies.

Statin Therapy and Lipid Indices in Chronic Kidney Disease: A Systematic Review and Meta-analysis of Randomized Control Trials.

BACKGROUND: Several studies have demonstrated the improvement in serum lipoproteins by statins in patients with Chronic Kidney Diseases (CKDs), including End-Stage Renal Disease (ESRD). However, the results of these studies are inconclusive. AIMS: We aimed to systematically investigate the effect of statins on lipid profiles of patients with CKD by performing a meta-analysis of Randomized Controlled Trials (RCTs). METHODS: Major electronic databases (Scopus, MEDLINE/PubMed, and ISI Web of Science) were searched from inception to August, 2023, to find randomized controlled trials (RCTs) evaluating the effect of different statins on serum lipoproteins in CKD patients. Weighted Mean Difference (WMD) with 95% Confidence Intervals (CI) was used to estimate the effect size. Trial Sequential Analysis (TSA) was performed to confirm the robustness of the evidence. RESULTS: A total of 18 publications were identified. It was found that statins reduced serum levels of Low-Density Lipoprotein (LDL)-C (WMD = -27.81 mg/dl, 95% CI = -34.47 to -21.15, P < 0.001) and total cholesterol (WMD = -25.44 mg/dl, 95% CI = -34.71 to -16.18, P < 0.001) in patients with CKD compared to the control group. Nonetheless, the effect of statins on High-Density Lipoprotein (HDL)-C (WMD = 0.57 mg/dl, 95% CI = -0.71 to 1.85, P = 0.38) and triglyceride (TG) (WMD = -9.08 mg/dl, 95% CI = -22.22 to 2.06, P = 0.11) was not statistically significant. The results of TSA confirmed the robustness of the evidence and were consistent with the pooled effect size. The findings of subgroup analysis and time response analysis were also significant. CONCLUSION: It was found that statin therapy reduced the levels of LDL-C and total cholesterol in patients with CKD.

Effect of Statins on Serum level of hs-CRP and CRP in Patients with Cardiovascular Diseases: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Several studies have reported that statins have anti-inflammatory effects. Nevertheless, results of clinical trials concerning the effect of statins on the levels of C-reactive protein (CRP) and high-sensitivity CRP (hs-CRP) have been inconsistent. Therefore, we performed a systematic review and meta-analysis of randomized clinical trials (RCTs) evaluating the effect of statins on CRP and hs-CRP levels in patients with cardiovascular diseases (CVDs). METHODS: Literature search of the major databases was performed to find eligible RCTs assessing the effect of statins on serum levels of CRP and hs-CRP from the inception until the last week of April 2021. The effect sizes were determined for weighted mean difference (WMD) and 95% confidence intervals (CI). RESULTS: 26 studies were identified (3010 patients and 2968 controls) for hs-CRP and 20 studies (3026 patients and 2968 controls) for CRP. Statins reduced the serum levels of hs-CRP (WMD = -0.97 mg/L; 95% CI: -1.26 to -0.68 mg/L; P < 0.001) and CRP (WMD = -3.05 mg/L; 95% CI: -4.86 to -1.25 mg/L; P < 0.001) in patients with CVDs. Statins decreased the serum levels of hs-CRP in patients receiving both high-intensity and moderate/low-intensity treatments with these drugs. In addition, the duration of treatment longer than 10 weeks decreased hs-CRP levels. Only high-intensity statin treatment could marginally decrease serum levels of CRP in CVDs patients. CONCLUSIONS: This meta-analysis showed the efficacy of statins to reduce the concentrations of CRP and hs-CRP in patients with different types of CVDs.

Effect of statins on the plasma/serum levels of inflammatory markers in patients with cardiovascular disease; a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: The anti-inflammatory properties of statins have been suggested by several researches. However, clinical trials have reported incongruous findings regarding the effect of statins on the levels of inflammatory markers other than high-sensitive C-reactive protein. Therefore, a systematic review and meta-analysis of randomized clinical trials were conducted to illuminate the effect of statins on serum levels of TNF-α, MCP-1, VCAM1, and IL-6 in patients with cardiovascular diseases (CVDs). METHODS: To find eligible studies, a systematic literature search of the main databases were conducted up to July 2021. The calculation of the effect sizes was conducted by standardized mean difference (SMD) and 95% confidence intervals (CI). RESULTS: The pooled analyses revealed that statins significantly reduced the TNF-α concentration (SMD = - 0.99 pg/mL; 95% CI - 1.43 to - 0.55 pg/mL; P < 0.001). Regarding dosage, high intensity (SMD = - 0.65 pg/mL; 95% CI - 1.19 to - 0.10, P = 0.02) and moderate/low (SMD = - 1.16 pg/mL; 95% CI - 1.84 to - 0.47, P = 0.001) intensity statins significantly decreased TNF-α levels. Moderate/low intensity statins administration in < 10 weeks treatment duration decreased serum level of TNF-α (SMD = - 0.91 pg/mL; 95% CI - 1.38 to - 0.44, P < 0.001). Lipophilic statins with high intensity dosage significantly decreased level of TNF-α (SMD = - 0.73 pg/mL; 95% CI - 1.43 to - 0.03, P = 0.04). Statins did not change serum levels of MCP-1, VCAM1, and IL-6 in CVD patients. CONCLUSIONS: The analyses indicated that statins have beneficial effects in decreasing serum levels of TNF-α in patients with CVDs.