The Effect of Enalapril on Anti-inflammatory Cytokines in Patients with Migraine: A Double-Blind, Randomized Clinical Trial

Document Type : Original Article (s)

Authors

1 Associate Professor, Physiology Research Center AND Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

2 Resident, Department of Ophthalmology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

3 Resident, Department of Cardiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: Migraine is one of the most common forms of headache. One of its possible mechanisms is neuro-inflammation in which some changes happen in inflammatory factors such as interleukins, adhesion molecules or acute phase reactants. On the other hand, one of the mechanisms by which angiotensin converting enzyme inhibitors (ACEIs) affect is anti-inflammation. The goal of this study was to evaluate the effect of enalapril on anti-inflammatory cytokines of patients with migraine.Methods: In this randomized double-blind placebo-controlled clinical trial, 10 mg enalapril daily was compared with matched placebo in 40 patients with migraine for two months. Serum IL-4, IL-10 and IL-13 levels were measured in all patients at 0 and 2 month.Findings: The serum level of IL-4 (P = 0.001), IL-10 (P < 0.001) and IL-13 (P < 0.001) increased significantly in the case group after treatment with enalapril.Conclusion: Enalapril may be effective in improvement of inflammatory responses in patients with migraine. This improvement could be the result of anti-inflammatory cytokines and may reduce the cerebrovascular risks in these patients.

Keywords


  1. Adams RD. Headache and other craniofacial pains. In: Adams RD, editor. Adams and victor's Principles of neurology. 7th ed. New York, NY: McGraw-Hill; 2000. p. 181-3.
  2. Lance YW. Headache and face pain: migraine. In: Swash M, Oxbury J, editors. Clinical neurology. 1st ed. Edinburgh, Scotland: Churchill Livingstone; 1991. p. 326-51.
  3. Lipton RB, Stewart WF. Prevalence and impact of migraine. Neurol Clin 1997; 15(1): 1-13.
  4. Lipton RB, Scher AI, Kolodner K, Liberman J, Steiner TJ, Stewart WF. Migraine in the United States: epidemiology and patterns of health care use. Neurology 2002; 58(6): 885-94.
  5. Silva FA, Rueda-Clausen CF, Silva SY, Zarruk JG, Guzman JC, Morillo CA, et al. Endothelial function in patients with migraine during the interictal period. Headache 2007; 47(1): 45-51.
  6. Markowitz S, Saito K, Moskowitz MA. Neurogenically mediated leakage of plasma protein occurs from blood vessels in dura mater but not brain. J Neurosci 1987; 7(12): 4129-36.
  7. Saito K, Markowitz S, Moskowitz MA. Ergot alkaloids block neurogenic extravasation in dura mater: proposed action in vascular headaches. Ann Neurol 1988; 24(6): 732-7.
  8. Buzzi MG, Moskowitz MA. The antimigraine drug, sumatriptan (GR43175), selectively blocks neurogenic plasma extravasation from blood vessels in dura mater. Br J Pharmacol 1990; 99(1): 202-6.
  9. Stovner LJ. Migraine prophylaxis with drugs influencing the renin-angiotensin system. Eur J Neurol 2007; 14(7): 713-4.
  10. Goadsby PJ. Emerging therapies for migraine. Nat Clin Pract Neurol 2007; 3(11): 610-9.
  11. Headache Classification Subcommittee of the International Headache Society. The international classification of headache disorders: 2nd edition. Cephalalgia 2004; 24(Suppl 1): 9-160.
  12. Javanmard SH, Sonbolestan SA, Heshmat-Ghahdarijani K, Saadatnia M, Sonbolestan SA. Enalapril improves endothelial function in patients with migraine: A randomized, double-blind, placebo-controlled trial. J Res Med Sci 2011; 16(1): 26-32.
  13. Ramadan NM. Current trends in migraine prophylaxis. Headache 2007; 47(Suppl 1): S52-S57.
  14. Silberstein SD. Preventive treatment of migraine. Trends Pharmacol Sci 2006; 27(8): 410-5.
  15. Ito H, Takemori K, Suzuki T. Role of angiotensin II type 1 receptor in the leucocytes and endothelial cells of brain microvessels in the pathogenesis of hypertensive cerebral injury. J Hypertens 2001; 19(3 Pt 2): 591-7.
  16. Tronvik E, Stovner LJ, Schrader H, Bovim G. Involvement of the renin-angiotensin system in migraine. J Hypertens Suppl 2006; 24(1): S139-S143.
  17. Fox KM. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet 2003; 362(9386): 782-8.
  18. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. Lancet 2001; 358(9287): 1033-41.
  19. Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000; 342(3): 145-53.
  20. Kothari SA, Le MK, Gandhi PJ. Effects of angiotensin converting enzyme inhibitors on thrombotic mediators: potential clinical implications. J Thromb Thrombolysis 2003; 15(3): 217-25.
  21. Schindler R, Dinarello CA, Koch KM. Angiotensin-converting-enzyme inhibitors suppress synthesis of tumour necrosis factor and interleukin 1 by human peripheral blood mononuclear cells. Cytokine 1995; 7(6): 526-33.
  22. Ridker PM. Inflammation, atherosclerosis, and cardiovascular risk: an epidemiologic view. Blood Coagul Fibrinolysis 1999; 10(Suppl 1): S9-12.
  23. Ridker PM. On evolutionary biology, inflammation, infection, and the causes of atherosclerosis. Circulation 2002; 105(1): 2-4.
  24. Liuzzo G, Biasucci LM, Gallimore JR, Grillo RL, Rebuzzi AG, Pepys MB, et al. The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina. N Engl J Med 1994; 331(7): 417-24.
  25. Guzman L. A new therapeutic target in atherosclerotic coronary artery disease: is the inhibition of the renin-angiotensin aldosteron system anti-ischemic?. Rev Fed Arg Cardiol 2000; 29: 305-12. [In Spanish].
  26. Lopez-Jaramillo P, Casas JP. Blockade of endothelial enzymes: new therapeutic targets. J Hum Hypertens 2002; 16(Suppl 1): S100-S103.
  27. Benveniste EN. Inflammatory cytokines within the central nervous system: sources, function, and mechanism of action. Am J Physiol 1992; 263(1 Pt 1): C1-16.
  28. Chapman PB, Lester TJ, Casper ES, Gabrilove JL, Wong GY, Kempin SJ, et al. Clinical pharmacology of recombinant human tumor necrosis factor in patients with advanced cancer. J Clin Oncol 1987; 5(12): 1942-51.
  29. Kemper RH, Meijler WJ, Korf J, Ter Horst GJ. Migraine and function of the immune system: a meta-analysis of clinical literature published between 1966 and 1999. Cephalalgia 2001; 21(5): 549-57.
  30. Empl M, Sostak P, Riedel M, Schwarz M, Muller N, Forderreuther S, et al. Decreased sTNF-RI in migraine patients? Cephalalgia 2003; 23(1): 55-8.
  31. Terwindt GM, Ferrari MD, Tijhuis M, Groenen SM, Picavet HS, Launer LJ. The impact of migraine on quality of life in the general population: the GEM study. Neurology 2000; 55(5): 624-9.
  32. Mortimer MJ, Kay J, Gawkrodger DJ, Jaron A, Barker DC. The prevalence of headache and migraine in atopic children: an epidemiological study in general practice. Headache 1993; 33(8): 427-31.
  33. Jeanjean AP, Moussaoui SM, Maloteaux JM, Laduron PM. Interleukin-1 beta induces long-term increase of axonally transported opiate receptors and substance P. Neuroscience 1995; 68(1): 151-7.
  34. Cunha FQ, Poole S, Lorenzetti BB, Ferreira SH. The pivotal role of tumour necrosis factor alpha in the development of inflammatory hyperalgesia. Br J Pharmacol 1992; 107(3): 660-4.
  35. Vale ML, Marques JB, Moreira CA, Rocha FA, Ferreira SH, Poole S, et al. Antinociceptive effects of interleukin-4, -10, and -13 on the writhing response in mice and zymosan-induced knee joint incapacitation in rats. J Pharmacol Exp Ther 2003; 304(1): 102-8.
  36. Yao MZ, Gu JF, Wang JH, Sun LY, Lang MF, Liu J, et al. Interleukin-2 gene therapy of chronic neuropathic pain. Neuroscience 2002; 112(2): 409-16.
  37. Perini F, D'Andrea G, Galloni E, Pignatelli F, Billo G, Alba S, et al. Plasma cytokine levels in migraineurs and controls. Headache 2005; 45(7): 926-31.
  38. Munno I, Marinaro M, Bassi A, Cassiano MA, Causarano V, Centonze V. Immunological aspects in migraine: increase of IL-10 plasma levels during attack. Headache 2001; 41(8): 764-7.
  39. Martelletti P, Stirparo G, Morrone S, Rinaldi C, Giacovazzo M. Inhibition of intercellular adhesion molecule-1 (ICAM-1), soluble ICAM-1 and interleukin-4 by nitric oxide expression in migraine patients. J Mol Med (Berl) 1997; 75(6): 448-53.