Mazur L. P.

CLINICAL AND EXPERIMENTAL MEDICINE

Scentific article

According to a number of studies, α-TNF has cytotoxic effect regarding beta-cells of Langerhans islets of the pancreas. Also high levels of this cytokine in patients with newly diagnosed type 1 diabetes was found. The content of α-TNF still high for the complete disappearance of the functional activity of the beta cells, allowing hypothesize about the association of hyperglycemia with persistent chronic inflammation. However, it remains understudied problem of balance and relationship between components of α-TNF and its role in the development of the diabetes types 1 and 2 and its chronic complications. The aim of the study was to evaluate the concentration of α-TNF in patients with diabetes and the number of blood cells, which carry the α-TNF first type membrane-bound receptor, and to assess their dependence on the type, severity of diabetes and degree of glycaemia compensation. Materials and methods. Were examined 83 patients with type 1 and 89 – with type 2 diabetes mellitus. The α-TNF concentration was performed using solid-phase immunoenzymatic method. The number of blood cells, which carry the α-TNF first type membrane-bound receptor was evaluated by laser flow cytometry. Results and discussion. Analyzing the received data pronounced activation of systemic inflammation and increased content of α-TNF, as key component in patients with type 2 diabetes was found. Obviously, this feature is caused by a combination in the pathogenesis of type 2 diabetes of various mutually aggravating mechanisms and metabolic disorders. In all groups of patients with diabetes was founded increased concentration of α-TNF in serum. In DM type 1 cytokine levels were (79,16 ± 1,94) pg/ml, with type 2 diabetes – (81,82 ± 2,11) pg/ml. In studying the dependence of increasing concentrations of α-TNF on the severity of type 2 diabetes it was found its substantial increase in patients with severe disease. The concentration of α-TNF significantly increased in patients with severe type 2 diabetes. Number of TNF-R1 cells in patients with type 1 diabetes increased to (69,72 ± 6,18) %, and to (27,42 ± 3,15) % – with compensation, and to (53,60 ± 5,34) % – with decompensation of type 2 DM. Levels of α-TNF and TNF-number P1 cells correlated with compensation of diabetes mellitus and significantly increased in the case of unsatisfactory glycaemia compensation. It should be noted that the number of TNF-R1 cells is also dependent on the severity of the underlying disease, the highest rates were observed in patients with severe disease, increasing 7,3 times compared with the control and 3,1 times – compared with a group of patients with an average severity of type 2 diabetes (p < 0. 001). Conclusions. The condition of the system of α-TNF and cells, which carry membrane-bound fraction of TNF-R1, dynamically changes, as an important primary component of the autoimmunity, in type 1 diabetes mellitus, and to some extent, as a compensatory mechanism for «metabolic immunodeficiency», in type 2 DM.

diabetes mellitus, α-TNF, α-TNF receptor type one

• Амбросова Т. М. Роль фактору некрозу пухлин-α при коморбідності артеріальної гіпертензії та ожиріння / Т. М. Амбро- сова // Світ медицини та біології. – 2013. – № 4. – С. 121-125.
• Прохоренко Т. С. Система фактора некроза опухолей α в патогенезе аутоиммунного сахарного диабета / Т. С. Прохо- ренко, Саприна Т. В., Лазаренко Ф. Э. [и др.] // Бюллетень сибирской медицины. – 2011. – № 1. – С. 64-70.
• Brodie G. M. B-cells promote intra-islet CD8+ cytotoxic T-cell survival to enhance type 1 diabetes / G. M. Brodie, M. Wallberg, P. Santamaria, F. S. Wong, E. A. Green // Diabetes. – 2008. – Vol. 57 (4). – P. 909–917.
• Dandona P. Inflammation: the link between insulin resistance, obesity and diabetes / P. Dandona, A. Aljada, A. Bandyopadhyay // Trends Immunol. – 2004. – Vol. 25. – P. 4–7.
• Festa A. Chronic subclinical inflammation as part of the insulin resistance syndrome: the Insulin Resistance Atherosclerosis Study (IRAS) / A. Festa, R. Jr. D’Agostino, G. Howard [et al.] // Circulation. – 2000. – Vol. 102. – P. 42–47.
• Garcнa-Compeбn D. І. Plasma cytokine levels imbalance in cirrhotic patients with impaired glucose tolerance and diabetes mellitus. A prospective study / D. І. Garcнa-Compeбn, J. O. Jбquez-Quintana, F. J. Lavalle-Gonzбlez [et al.] // Ann. Hepatol. 2014. – – Vol. 13 (4). – P. 403-410.
• Joussen A. M. TNF-α mediated apoptosis plays an important role in the development of early diabetic retinopathy and long- term histopathological alterations / A. M. Joussen, S. Doehmen, M. L. Le [et al.] // Molecular Vision. – 2009. – – Vol. 15. – P. 1418–1428.
• Jung D. -S. Apoptosis occurs differentially according to glomerular size in diabetic kidney disease / D. -S. Jung, S. H. Lee, S. -J. Kwak [et al.] // Nephrology Dialysis Transplantation. – 2012. – Vol. 27 (1). – P. 259–266.
• Kьhtreiber W. M. Central role of defective apoptosis in autoimmunity / W. M. Kьhtreiber, T. Hayashi, E. A. Dale, D. L. Faustman // Journal of Molecular Endocrinology . – 2003. – Vol. 31 (3). P. -373–399.
• Leijon K. Non-obese diabetic (NOD) mice display enhanced immune responses and prolonged survival of lymphoid cells / K. Leijon, B. Hammarstrom, D. Holmberg // International Immunology. – 1994. – – Vol. 6 (2). P. 339–345.
• Luo X. Immunotherapy of type 1 diabetes: where are we and where should we be going? / X. Luo, K. C. Herold, S. D. Miller // Immunity. – 2010. – – Vol. 39 (4). – P. 488–499.
• Mastrandrea L. Etanercept treatment in children with new-onset type 1 diabetes: pilot randomized, placebo-controlled, dou- ble-blind study / L. Mastrandrea, J. Yu, T. Behrens [et al.] // Diabetes Care. – 2009. – – Vol. 39 (7). – P. 1244–1249.
• Peters M. J. Etanercept treatment in children with new-onset type 1 diabetes: pilot randomized, placebo-controlled, double- blind study: response to / M. J. Peters [et al.] // Diabetes Care. – 2009. – – Vol. 39 (12). – P. e153.
• Phillips C. M. Does inflammation determine metabolic health status in obese and nonobese adults? / C. M. Phillips, I. J. Perry // J. Clin. Endocrinol. Metab. – 2013. – Vol. 98. – P. E1610–E1619.
• Shi Y. The global implications of diabetes and cancer / Y. Shi, F. B. Hu // The Lancet. – 383 (9933). – P. 1947–1948.
• Wellen K. E. Inflammation, stress and diabetes / K. E. Wellen, G. S. Hotamisligil // J. Clin. Invest. – 2005. – Vol. 115. – P. 1111–1119.

«Bulletin of problems biology and medicine» Issue 4 part 1 (113), 2014 year, 156-159 pages, index UDK 616. 379-008. 64]- 616-092. 19