E.V. KHAZOVA¹, O.V. BULASHOVA¹, V.N. OSLOPOV¹, M.I. MALKOVA¹, D.A. ZAPLATOVA², E.A. KOLPAKOVA², V.M. GAZIZIANOVA¹

¹Kazan State Medical University, 49 Butlerov Str., Kazan, Russian Federation, 420012

²City Clinical Hospital No.7, 54 Chuykova Str., 54, Kazan, Russian Federation, 420132

 Khazova E.V. ― Cand. Med. Sc., Associate Professor of the Department of Propaedeutics of Internal Diseases, tel. +7-905-313-97-10, e-mail: hazova_elena@mail.ru

Bulashova O.V. ― D. Med. Sc., Professor of the Department of Propaedeutics of Internal Diseases, tel. (843) 296-14-03, e-mail: boulashova@yandex.ru

Oslopov V.N. ― D. Med. Sc., Professor, Head of the department of Propaedeutics of Internal Diseases, tel. +7-905-316-25-35, e-mail: kpvbol@yandex.ru

Malkova M.I. ― Cand. Med. Sc., Assistant of the Department of Propaedeutics of Internal Diseases, tel. +7-960-051-61-16, e-mail: marimalk@yandex.ru

Zaplatova D.A. ― physician of the therapeutic department, tel. +7-917-257-81-42

Kolpakova E.A. ― physician of the therapeutic department, tel. +7917-913-43-30

Gazizianova V.M. ― graduate student of the Department of Propaedeutics of Internal Diseases, tel. +7-927-037-73-41, e-mail: violettakoshka2006@rambler.ru

Prevention and treatment of chronic heart failure (CHF) remains to be a relevant medical and social problem. Detection of an increased level of pro-inflammatory cytokines that have a number of negative effects in blood of patients with heart failure, regardless of its etiology, allowed to formulate an immunoinflammatory concept of the pathogenesis of chronic heart failure. Levels of TNF-alpha, IL-1b and IL-6 correlate with the severity of clinical manifestations, as well as the activity of neurohumoral background in heart failure patients. Circulating levels of inflammatory cytokines (TNF-alpha and IL-6) and cytokine receptors are recognized as independent predictors of mortality in patients with severe heart failure. There was made a review of international studies of new classes of drugs ― TNF-α synthesis inhibitors or inhibitors of TNF-α activity. The article highlights the positive effect on the immune system of the body made by such classical means of treating heart failure as ACE inhibitors, blockers of angiotensin II receptors, beta-blockers.

Key words: heart failure, tumor necrosis factor, systemic inflammation.

REFERENCES

1. Packer M. The neurohumoral hykhothesis: a theory to explain the mechanism of disease progression in heart failure. J.Am.Coll.Cardiol, 1992, no. 20, rr. 248-254.
2. Wu C.K., Lee J.K., Chiang F.T. et al. Plasma levels of tumor necrosis factor-α and interleukin-6 are associated with diastolic heart failure through downregulation of sarcoplasmic reticulum Ca2+ ATPase. Crit Care Med, 2011, no. 39(5), rr. 984-92.
3. Hedayat M. Proinflammatory cytokines in heart failure: double-edget swords. Heart Fail. Rev, 2010, vol. 15, no. 6, pp. 543-562.
4. Arai K., Lee F., Miyajima A. et al. Cytokines:coordinators of immune and inflammatory responses. Ann. Rev. Biochem, 1990, no. 59, rr. 783.
5. Wei C.M., Lerman A., Rodeheffer R.J. et al. Endothelin in human congestive heart failure. Circulation, 1994, no. 89, rr. 1580-1586.
6. Seta Y., Shan K., Bozkurt B. et al.  Basic mechanisms in heart failure: the cytokine hypothesis. J.Cardiac Failure, 1996, no.2, rr.243-249.
7. Costelli P., Carbo N., Tessotore L. et al. Tumor necrosis factor-alfa mediated changes in tissue protein turnover in rat cancer cachexia modek. J. Clin. Inves, 1993, no. 92, rr. 2783-2789.
8. Yokoyama T., Nakano M., Bednerczyk J.L. et al. Tumor necrosis factor-alfa provokes a hypertrophic growth response in adult cardiac myocytes. Circulation, 1997, no. 95, rr. 1247-1252.
9. Finkel M.S., Oddis C.V., Jacob T.D. et al.  Negative inotropic effects of cytokines on the heart mediated by nitric oxide. Science, 1992, no. 257, rr. 387-389.
10. Levine B., Kalman J., Mayer L. et al. Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. N Engl J Med, 1990, no. 323(4), rr. 236-41.
11. Teasta M., Yeh M., Lee P. et al. Circulating levels of cytokines and their endogenous modulators in patients with mild to severe congestive heart failure due to coronary artery disease or hypertension. J Am Coll Cardiol, 1996, no. 28, rr. 964-71.
12. Ferrari R., Bachetti T., Confortini R. et al. Tumor necrosis factor soluble receptors in patients with various degrees of congestive heart failure. Circulation, 1995, no. 92, rr. 1479-86.
13. Kalogeropoulos A., Georgiopoulou V., Psaty B.M. Inflammatory markers and incident heart failure risk in older adults: the Health ABC (Health, Aging, and Body Composition) study.Health FDC Study Health ABC Study Investigators. J Am Coll Cardiol, 2010, no. 55(19), rr. 2129-37.
14. Torre-Amione G., Kapadia S., Benedict C. et al. Proinflammatory cytokine levels in patients with depressed left ventricular ejection fraction: a report from the Studies Of Left Ventricular Dysfunction (SOLVD). J. Am. Coll. Cardiol, 1996, no. 27, rr. 1201-1206.
15. Blum A., Miller H. Role of cytokines in heart failure. Am Heart J, 1998, no. 135, rr. 181-186.
16. Cohn J.H., Goldstein S.O., Greenberg B.H. A dose-dependent increase in mortality with vesnarinone among patients with severe heart failure. Vesnarinone Trial Investigators. New Engl. J. Med, 1998, vol. 339, pp. 1810-1816.
17. Deswal A., Petersen N.J., Feldman A.M. et al. Cytokines and cytokine receptors in advanced heart failure: an analysis of the cytokine database from the VESnarinone Trial (VEST). Circulation, 2001, vol. 103, pp. 2055-2059.
18. Rauchhaus M., Dohner W., Koloczek V. et al. Systemically measured cytokines are independently predictive for increased mortality in patients with chronic heart failure. J Am Coll Cardiol, 2000, no. 35 (Suppl. A), r. 1183.
19. Nasonov E.L., Samsonov M.Yu., Belenkov Yu.N. et al. Immunopathology of congestive heart failure: the role of cytokines. Kardiologiya, 1999, no. 3, pp. 66-73 (in Russ.).
20. Deswal A., Petersen N.J., Feldman A.M. et al. Effects of vesnarinone on peripheral circulating levels of cytokines and cytokine receptors in patients with heart failure: a report from the Vesnarinone Trial. Chest, 2001, no.120, rr. 453-459.
21. Bozkurt B., Torre-Amione G., Warren M.S. et al. Results of targeted anti¬tumor necrosis factor therapy with etanercept (ENBREL) in patients with advanced heart failure. Circulation, 2001, no. 103, rr. 1044-1047.
22. Kadokami T., McTiernan C.F., Kubota T. et al. Effects of soluble TNF receptor treatment on lipopolysaccaride-induced myocardial cytokine expression. Amer. J. Physiology, 2001, vol. 280, pp. 2281-2291.
23. Louis A., Cleland J.G., Crabbe S. et al.  Clinical trials update. Europ. J. Heart Fail, 2001, vol. 3, pp. 381-387.
24. Coletta A.P., Clark A.L., Banarjee P. et al. Clinical trials update: RENEWAL (RENAISSANCE and RECOVER) and ATTACH. Eur J Heart Fail, 2002, no.4, rr. 559–561.
25. Chung E.S., Packer M., Lo K.H. et al. Randomized, double-blind, placebo- controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure: results of the anti-TNF Therapy Against Congestive Heart Failure (ATTACH) trial. Circulation, 2003, no.107, rr. 3133–3140.
26. Sliwa K., Woodiwiss A., Candy G. et al.  Effects of pentoxifylline on cytokine profile sand left ventricular performance in patients with decompensated congestive heart failure secondary to idiopathic dilated cardiomyopathy. J. Cardiol, 2002, no. 90(10), rr. 1118-22.
27. Sliwa K., Woodiwiss A., Kone V.N. et al. Therapy of ischemic cardiomyopathy with the immunomodulating agent pentoxifylline: results of a randomized study. Circulation, 2004, no. 109(6), rr. 750-5.
28. Samsonov M., Nassonov E., Werner-Felmayer G. et al.  Captopril and the effect of interferon gamma on monocytes. Arch Intern Med , 1993, no. 153, rr. 1138-42.
29. Liu L., Zhao S-P. The changes of circulating tumor necrosis factor levels in patients with congestive heart failure influenced by therapy. Intern J Cardiol, 1999, no.69, rr. 77-82.
30. Koller-Strametz J., Pacher R., Fery B. et al. Circulating tumor necrosis factor levels in chronic heart failure: relation to its soluble receptor II, interleukin-6 and neurohumoral variables.J Heart Lung transplant. –1998, no. 17, rr. 356-62.
31. Tsutamoto T., Wada A., Maeda K. et al. Angiotensin II type receptor antagonist decreases plasma levels of tumor necrosis factor alpha, interleukin-6 and soluble adhesion molecules in patients with chronic heart failure. J Am Coll Cardio, 2000, no. 35, rr. 714-21.