Authors
Galstyan K.О.,1 Nedosugova L. V.,1 Zemlyanoj A.B.,2 Kolmychkova K. I.,3 Sobenin I. A.4
1. Endocrinology department, Medical Faculty, Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow.
2. Department of Surgical infections, Federal state budgetary institution “National Medical and Surgical Center named after N.I. Pirogov” of the Ministry of Healthcare of the Russian Federation, Moscow.
3. Autonomous non-profit organization Research Institute of Atherosclerosis of the Russian Academy of Natural Sciences, Moscow.
4. Federal State budget organization National medical research center of cardiology of the Ministry of healthcare of the Russian Federation, Moscow.
Abstract
42 patients with diabetic foot syndrome (DFS), 14 patients with a neuropathic form (7m / 7f), 28 with a neuroischemic (22m / 6f) were examined. The levels of basal and interferon-ɣ stimulated TNF-α secretion, CCL18- interleukin-4 monocyte-macrophages with various ulcerative defects were studied by ELISA. In patients with neuropathic form of DFS, we found higher values of the proinflammatory response and a significant decrease in the stimulated anti-inflammatory response, compared with patients with the neuroischemic form (p <0.001). Excess production of TNF-α and a decrease in CCL18 were detected in patients with a duration of ulcerative defects more than 6 months, (p <0.05). In patients with defects of small and large sizes (<1 cm2,> 3 cm2), higher values of TNF-α, p <0.001, than in patients with defects of medium size (1-3 cm2). With defects of 1-3 cm2, no stimulatory anti-inflammatory response was obtained, and in patients with ulcers <1 cm2, the stimulated response is lower than basal. In this cohort, a correlation was found between a high level of HbA1c> 8.0% and a low level of CCL18 (r = -0.883; p = 0.008). In patients with DFS, the imbalance M1 / M2 of monocyte-macrophage activation is noted in patients with chronic hyperglycemia, which leads to untimely switching of phenotypes, as a result, reparative processes are suppressed, which is a criterion for the unfavorable course of the wound process and a negative prognosis for the healing of the defect.
Keywords: DFS, ulcerative defect, anti-inflammatory cytokine, anti-inflammatory chemokine, polarization of macrophage.
References
1. Anciferov M.B. Sindrom diabeticheskoj stopy: klinika, diagnostika, lechenie i profilaktika/ M.B.Anciferov, G.R. Galstyan, A.YU.Tokmakova, I.I. Dedov// Saharnyj diabet.-2001.№2.- S2-8;67-73.
2. Anciferov, M.B. Sindrom diabeticheskoj stopy /M.B. Anciferov, E. YU. Komelyagina.-M.: Medicinskoe informacionnoe agentstvo, 2013.-14-15s.
3. Bakker K. Profilaktika i lechenie zabolevanij stopy pri diabete. /K.Bakker, Dzh.Apel'kvist, B.A.Lipski i dr. perevod s angl. I.V.Gurevoj i M.A.Dadyana//Rukovodstvo, dokumenty i rekomendacii (mezhdunarodnyj konsensus po diabeticheskoj stope).-2015.S.4.
4. Bregovskij V.B. Diabeticheskaya distal'naya polinejropatiya. Obzor sovremennyh rekomendacij/ V.B.Bregovskij, V.N.Hramilin,I.YU.Demidova// Annaly klinicheskoj i ehksperimental'noj nevrologii.-2015.-tom.9.№1.S.60-68.
5. Vajntraub, B.D. Molekulyarnaya ehndokrinologiya/ B. D. Vajntraub.- Fundamental'nye issledovaniya i ih otrazhenie v klinike,2003.- 262-265s.
6. Gur'eva I.V. Sovremennye podhody k opredeleniyu, diagnostike i klassifikacii diabeticheskoj polinejropatii, Patogeneticheskie aspekty lecheniya / I.V. Gur'eva, YU.S. Onuchina// Consilium medicum.-2016.-№12.-S.103-109.
7. Dedov, I.I.Saharnyj diabet: ostrye i hronicheskie oslozhneniya/ I.I. Dedov, M.V. SHestakova.- M.:Medicinskoe informacionnoe agentstvo, 2012.- 365-403s.
8. Kuzina M.I. Rany i ranevaya infekciya/ M.I. Kuzina, B.M. Kostyuchenok.- Rukovodstvo dlya vrachej.-M.: Medicina, 1990.-97s.
9. Komelyagina E.V., Kliniko-morfologicheskie parametry i markery reparacii nefropaticheskih yazvennyh defektov pri sindrome diabeticheskoj stopy/ E.V.Komelyagina, E.A.Kogan, M.B.Anciferov//Saharnyj diabet.-2015;18(3).S.70-76.
10. Lyamina, S.V. Polyarizaciya makrofagov v sovremennoj koncepcii formirovaniya immunnogo otveta/S.V Lyamina., I.YU. Malyshev// ZHurnal Fundamental'nye issledovaniya.-2014.-№10.-930-935s.
11. Savel'ev V.S. Klinicheskaya hirurgiya/ V.S. Savel'ev, A.I. Kirienko.-M.: GEHOTAR-Media, 2008.-T.1.-537s.
12. Simbircev A.S. Lechebnoe primenenie citokinov/A.S. Simbircev.-SPb.:RIC PSPbGMU,2017.-4s.
13. SHol'c. N. Podologiya/ Uchebnik i illyustrirovannyj atlas po podologii//N. SHCHol'c, 2017.-322s.
14. Bodnar, R.J. Chemokine Regulation of During Wound Healing / R.J. Bodnar// Ady Wound Care(New Rochelle).-2015.-4(11).-P.641-650.
15. Blaser, H. TNF and ROS Crosstalk in Inflammation/ H. Blaser, D. Brenner, C.Dostert//Journal Cellpress,2016. –P.1-13.
16. Brennan, M.B. Diabetic foot ulcer severity predicts mortality among veterans with type 2 diabetes/ M.B. Brennan, T.M. Hess, В.Bartle, Cooper J.M. et al.// Journal of diabetes and its complications, 2017.-N.31(3).-Р.556-561.
17. Macleod, A.S. The Innate Immune System in Acute and chronic wounds/ A.S. Macleod, J.N. Mansbridge//Ady Wound Care(New Rochelle).-2016.-5(2).-P.65-78.
18. Van Netten J. J. Prevention of foot ulcers in the at-risk patient with diabetes/ J. J. Van Netten, P. E. Price, L. A. Lavery et al.// Diabetes.Metabolism research and reviews, 2016.-32(Suppl.1).-P.84–98.
19. Werner, S. Regulation of wound healing by growth factors and cytokines/ S.Werner, R.Grose// Physiol Rev, 2003.-83(3).-P.835-70.
