Anti-inflammatory effect of colchicine in Japanese patients with stable coronary artery disease: A pilot study

Background. Promising results regarding potential anti-inflammatory and antiatherosclerotic effects of gliptins have been reported. Our aim was to investigate whether saxagliptin treatment modifies expression of inflammatory markers, primarily in peripheral blood mononuclear cells (PBMCs) and in circulating leukocytes in patients with stable coronary artery disease (CAD) and T2DM. Methods. Patients (n=12) were randomized to saxagliptin 5 mg daily or placebo for 3 months. Samples were taken at baseline and end of study in fasting state prior to intake of medications. PBMCs were isolated and cryopreserved at −150°C until ex vivo exposed to 1 ng/mL of lipopolysaccharide (LPS) for 4 hours. Gene expression was performed with custom-designed TaqMan® Arrays and relative quantification by real-time PCR (RT-qPCR). Results. HbA1c was reduced in the saxagliptin-treated group compared to that in the change with placebo (p=0.042). In unstimulated PBMCs and in circulating leukocytes, we observed a significant increase in IL-10 expression in the saxagliptin group (p=0.043, both), significantly different from that in the placebo (p=0.009 and p=0.032, resp.). No between group differences in changes were observed in any of the selected proinflammatory markers. Conclusion. In our small cohort of patients with combined T2DM and CAD, a possible anti-inflammatory effect of saxagliptin, observed in the present study by upregulation of IL-10 in leukocytes, needs to be confirmed in larger studies.

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Abstract 2872: Interleukin-18/interleukin-10 Ratio is an Independent Predictor of Cardiovascular Events in Patients with Stable Coronary Artery Disease

Circulation ◽

10.1161/circ.116.suppl_16.ii_639-c ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Paulo V Camargo ◽

Raquel M Roman ◽

Ana Paula W Rossini ◽

Anderson Dedonelli ◽

Steffan F Stella ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Inflammatory Cytokine ◽

Stable Coronary Artery Disease ◽

Vascular Event ◽

Coronary Syndrome ◽

Anti Inflammatory ◽

Hs Crp ◽

Artery Disease ◽

Stable Cad

Background: The balance between pro-inflammatory cytokine IL-18 and anti-inflammatory cytokine IL-10 has been suggested to play a role in atherogenesis and in the prognosis of acute coronary syndrome (ACS). We hypothesized that stable coronary artery disease (CAD) patients have a pro-inflammatory profile prior to an acute event. Methods : A case-control study nested in a cohort of stable CAD patients was performed. Patients were consecutively included and blood samples collected at 3-months intervals. Cases were patients who presented any vascular event (death, ACS, ischemic stroke, peripheral arterial occlusion and revascularization) and controls were retrieved from a sequential list, in a 1:2 ratio, after 22 ± 9 months of follow-up. Serum hs-CRP, interleukin (IL)-10, IL-18 were measured in two serial samples, collected before the events. Results : Among 176 CAD patients, 42 developed a vascular event (cases) and 76 were selected to the control group. Serum levels of IL-18 were significantly higher among cases (411 ± 185 vs. 340 ± 133pg/ml; p = 0.037). Hs-CRP levels (5.4 vs. 5.1mg/l), IL-10 (7.4 vs. 7.2pg/ml), and IL-18/IL-10 ratio (66 vs. 61) were not different between cases and controls in both samples. Cox regression analysis showed that IL-18 levels (HR 1.75 (0.89 –3.5;p = 0.11) and IL-18/IL-10 ratio (HR 1.97; 1.0 –3.8) were predictors of worse prognosis (Figure ). Conclusion: In this study, IL-18 and IL-18/IL-10 ratio were associated with clinical outcomes and support the hypothesis that the balance between pro-inflammatory and anti-inflammatory cytokines may be an important determinant of vascular events in stable CAD patients.

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