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The phosphodiesterase 5 inhibitor sildenafil decreases the proinflammatory chemokine IL-8 in diabetic cardiomyopathy: in vivo and in vitro evidence

Authors
  • Giannattasio, S.1
  • Corinaldesi, C.1, 2
  • Colletti, M.1
  • Di Luigi, L.1
  • Antinozzi, C.1
  • Filardi, T.3
  • Scolletta, S.4
  • Basili, S.5
  • Lenzi, A.3
  • Morano, S.3
  • Crescioli, C.1
  • 1 Università degli Studi di Roma “Foro Italico”, Department of Movement, Human and Health Sciences, Section of Health Sciences, Unit of Endocrinology, Rome, 00135, Italy , Rome (Italy)
  • 2 University of Columbia, Institute for Cancer Genetics, New York, USA , New York (United States)
  • 3 Sapienza University of Rome, Department of Experimental Medicine, Policlinico Umberto I, Rome, Italy , Rome (Italy)
  • 4 University of Siena, Department of Medical Biotechnologies, Siena, Italy , Siena (Italy)
  • 5 Sapienza University of Rome, Department of Internal Medicine and Medical Specialties, Policlinico Umberto I, Rome, Italy , Rome (Italy)
Type
Published Article
Journal
Journal of Endocrinological Investigation
Publisher
Springer-Verlag
Publication Date
Nov 10, 2018
Volume
42
Issue
6
Pages
715–725
Identifiers
DOI: 10.1007/s40618-018-0977-y
Source
Springer Nature
Keywords
License
Green

Abstract

PurposeInterleukin (IL)-8 is a proinflammatory C-X-C chemokine involved in inflammation underling cardiac diseases, primary or in comorbid condition, such diabetic cardiomyopathy (DCM). The phosphodiesterase type 5 inhibitor sildenafil can ameliorate cardiac conditions by counteracting inflammation. The study aim is to evaluate the effect of sildenafil on serum IL-8 in DCM subjects vs. placebo, and on IL-8 release in human endothelial cells (Hfaec) and peripheral blood mononuclear cells (PBMC) under inflammatory stimuli.MethodsIL-8 was quantified: in sera of (30) DCM subjects before (baseline) and after sildenafil (100 mg/day, 3-months) vs. (16) placebo and (15) healthy subjects, by multiplatform array; in supernatants from inflammation-challenged cells after sildenafil (1 µM), by ELISA.ResultsBaseline IL-8 was higher in DCM vs. healthy subjects (149.14 ± 46.89 vs. 16.17 ± 5.38 pg/ml, p < 0.01). Sildenafil, not placebo, significantly reduced serum IL-8 (23.7 ± 5.9 pg/ml, p < 0.05 vs. baseline). Receiver operating characteristic (ROC) curve for IL-8 was 0.945 (95% confidence interval of 0.772 to 1.0, p < 0.01), showing good capacity of discriminating the response in terms of drug-induced IL-8 decrease (sensitivity of 0.93, specificity of 0.90). Sildenafil significantly decreased IL-8 protein release by inflammation-induced Hfaec and PBMC and downregulated IL-8 mRNA in PBMC, without affecting cell number or PDE5 expression.ConclusionSildenafil might be suggested as potential novel pharmacological tool to control DCM progression through IL-8 targeting at systemic and cellular level.

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