Vol 69, No 6 (2018)
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Published online: 2018-09-25

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The effect of short-term perindopril and telmisartan treatment on circulating levels of anti-inflammatory cytokines in hypertensive patients

Wojciech Gilowski1, Robert Krysiak2, Bogdan Marek34, Bogusław Okopień2
Pubmed: 30259507
Endokrynol Pol 2018;69(6):667-674.


Introduction: Both angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers were found to reduce plasma levels of proinflammatory cytokines. No previous study has compared their effect on the production of anti-inflammatory cytokines.
Material and methods: The study enrolled 52 patients with grade 1 and grade 2 arterial hypertension. The participants were divided into two groups treated with either perindopril (4 mg daily) or telmisartan (40 mg daily). Blood pressure, plasma lipids, glucose homeostasis markers, as well as plasma levels of uric acid, interleukins 4, 10, 13 (IL-4, IL-10, IL-13), and high sensitivity C-reactive protein (hsCRP)
were measured at the beginning of the study and six weeks later.
Results: Both perindopril and telmisartan reduced systolic (SBP) and diastolic blood pressure (DBP). Although both agents increased serum levels of IL-10, this effect was more pronounced in patients treated with telmisartan. Neither telmisartan nor perindopril affected circulating levels of uric acid, glucose, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, IL-4, IL-13, and hsCRP. The effect of telmisartan on IL-10 slightly correlated with an improvement in insulin sensitivity. Treatment-induced changes in IL-10 did not correlate
with hypotensive properties of perindopril and telmisartan.
Conclusions: The obtained results indicate that angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers administered for a short period of time produce a relatively week effect on anti-inflammatory cytokines, limited to IL-10, and stronger for telmisartan than for perindopril.

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  1. Oparil S, Acelajado MC, Bakris GL, et al. Hypertension. Nat Rev Dis Primers. 2018; 4: 18014.
  2. Poulter NR, Prabhakaran D, Caulfield M. Hypertension. Lancet. 2015; 386(9995): 801–812.
  3. Nosalski R, McGinnigle E, Siedlinski M, et al. Novel Immune Mechanisms in Hypertension and Cardiovascular Risk. Curr Cardiovasc Risk Rep. 2017; 11(4): 12.
  4. Mian MO, Paradis P, Schiffrin EL. Innate immunity in hypertension. Curr Hypertens Rep. 2014; 16(2): 413.
  5. Justin Rucker A, Crowley SD. The role of macrophages in hypertension and its complications. Pflugers Arch. 2017; 469(3-4): 419–430.
  6. Chen S, Agrawal DK. Dysregulation of T cell subsets in the pathogenesis of hypertension. Curr Hypertens Rep. 2015; 17(2): 8.
  7. Bautista LE, Vera LM, Arenas IA, et al. Independent association between inflammatory markers (C-reactive protein, interleukin-6, and TNF-alpha) and essential hypertension. J Hum Hypertens. 2005; 19(2): 149–154.
  8. Sung KiC, Suh JY, Kim BS, et al. High sensitivity C-reactive protein as an independent risk factor for essential hypertension. Am J Hypertens. 2003; 16(6): 429–433.
  9. Solak Y, Afsar B, Vaziri ND, et al. Hypertension as an autoimmune and inflammatory disease. Hypertens Res. 2016; 39(8): 567–573.
  10. Aronow WS, Frishman WH. Contemporary Drug Treatment of Hypertension: Focus on Recent Guidelines. Drugs. 2018; 78(5): 567–576.
  11. Di Raimondo D, Tuttolomondo A, Buttà C, et al. Effects of ACE-inhibitors and angiotensin receptor blockers on inflammation. Curr Pharm Des. 2012; 18(28): 4385–4413.
  12. Ferrario CM, Richmond RS, Smith R, et al. Renin-angiotensin system as a therapeutic target in managing atherosclerosis. Am J Ther. 2004; 11(1): 44–53.
  13. Deinum J, Chaturvedi N. The Renin-Angiotensin system and vascular disease in diabetes. Semin Vasc Med. 2002; 2(2): 149–156.
  14. Negro R. Endothelial effects of antihypertensive treatment: focus on irbesartan. Vasc Health Risk Manag. 2008; 4(1): 89–101.
  15. Fogari R, Zoppi A. Antihypertensive drugs and fibrinolytic function. Am J Hypertens. 2006; 19: 1293–1299.
  16. Hamilton TA, Ohmori Y, Tebo J. Regulation of chemokine expression by antiinflammatory cytokines. Immunol Res. 2002; 25(3): 229–245.
  17. Vitkovic L, Maeda S, Sternberg E. Anti-inflammatory cytokines: expression and action in the brain. Neuroimmunomodulation. 2001; 9(6): 295–312.
  18. Herder C, Carstensen M, Ouwens DM. Anti-inflammatory cytokines and risk of type 2 diabetes. Diabetes Obes Metab. 2013; 15 Suppl 3: 39–50.
  19. Dandona P, Dhindsa S, Ghanim H, et al. Angiotensin II and inflammation: the effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockade. J Hum Hypertens. 2007; 21(1): 20–27.
  20. McMaster WG, Kirabo A, Madhur MS, et al. Inflammation, immunity, and hypertensive end-organ damage. Circ Res. 2015; 116(6): 1022–1033.
  21. Opal SM, DePalo VA. Anti-inflammatory cytokines. Chest. 2000; 117(4): 1162–1172.
  22. Tedgui A, Mallat Z. Cytokines in atherosclerosis: pathogenic and regulatory pathways. Physiol Rev. 2006; 86(2): 515–581.
  23. Kinlay S, Egido J. Inflammatory biomarkers in stable atherosclerosis. Am J Cardiol. 2006; 98(11A): 2P–8P.
  24. Krysiak R, Okopień B. Different effects of perindopril and enalapril on monocyte cytokine release in coronary artery disease patients with normal blood pressure. Pharmacol Rep. 2012; 64(6): 1466–1475.
  25. Krysiak R, Okopień B. Lymphocyte-suppressing action of angiotensin-converting enzyme inhibitors in coronary artery disease patients with normal blood pressure. Pharmacol Rep. 2011; 63(5): 1151–1161.
  26. Krysiak R, Okopień B, Krysiak R, et al. Pleiotropic effects of angiotensin-converting enzyme inhibitors in normotensive patients with coronary artery disease. Pharmacol Rep. 2008; 60(4): 514–523.
  27. Han X, Boisvert WA. Interleukin-10 protects against atherosclerosis by modulating multiple atherogenic macrophage function. Thromb Haemost. 2015; 113(3): 505–512.
  28. Destro M, Cagnoni F, Dognini GP, et al. Telmisartan: just an antihypertensive agent? A literature review. Expert Opin Pharmacother. 2011; 12(17): 2719–2735.
  29. Rogowicz-Frontczak A, Majchrzak A, Zozulińska-Ziółkiewicz D. Insulin resistance in endocrine disorders - treatment options. Endokrynol Pol. 2017; 68(3): 334–351.
  30. Leon-Cabrera S, Arana-Lechuga Y, Esqueda-León E, et al. Reduced systemic levels of IL-10 are associated with the severity of obstructive sleep apnea and insulin resistance in morbidly obese humans. Mediators Inflamm. 2015; 2015: 493409.
  31. Taddei S, Bortolotto L. Unraveling the Pivotal Role of Bradykinin in ACE Inhibitor Activity. Am J Cardiovasc Drugs. 2016; 16(5): 309–321.
  32. Wang PH, Cenedeze MA, Campanholle G, et al. Deletion of bradykinin B1 receptor reduces renal fibrosis. Int Immunopharmacol. 2009; 9(6): 653–657.
  33. Siragy H. The role of the AT2 receptor in hypertension. Am J Hypertens. 2000; 13(5): S62–S67.
  34. Kaschina E, Namsolleck P, Unger T. AT2 receptors in cardiovascular and renal diseases. Pharmacol Res. 2017; 125(Pt A): 39–47.
  35. Dhande I, Ma W, Hussain T. Angiotensin AT2 receptor stimulation is anti-inflammatory in lipopolysaccharide-activated THP-1 macrophages via increased interleukin-10 production. Hypertens Res. 2015; 38(1): 21–29.
  36. Cardilo-Reis L, Gruber S, Schreier SM, et al. Interleukin-13 protects from atherosclerosis and modulates plaque composition by skewing the macrophage phenotype. EMBO Mol Med. 2012; 4(10): 1072–1086.
  37. Kuperman DA, Schleimer RP. Interleukin-4, interleukin-13, signal transducer and activator of transcription factor 6, and allergic asthma. Curr Mol Med. 2008; 8(5): 384–392.
  38. Wery-Zennaro S, Letourneur M, David M, et al. Binding of IL-4 to the IL-13Ralpha(1)/IL-4Ralpha receptor complex leads to STAT3 phosphorylation but not to its nuclear translocation. FEBS Lett. 1999; 464(1-2): 91–96.
  39. Kelly-Welch A, Hanson EM, Keegan AD. Interleukin-4 (IL-4) Pathway. Science Signaling. 2005; 2005(293): cm9–cm9.
  40. Kelly-Welch A, Hanson EM, Keegan AD, et al. Interleukin-13 (IL-13) pathway. Sci STKE. 2005; 2005(293): cm8.
  41. Krysiak R, Gdula-Dymek A, Marek B, et al. The effect of hypolipidemic treatment on monocyte cytokine release in different age groups of patients with type 2 diabetes and atherogenic dyslipidemia. Endokrynol Pol. 2016; 67(2): 190–196.