The level of circulating cytokines and chemokines in the preclinical and early clinical stages of development of type 1A diabetes mellitus


Cite item

Full Text

Abstract

Aim: to study the level of circulating proinflammatory (IL-1α, IL-1β, IL-6, α-TNF, IFN-γ) and anti-inflammatory (IL-4, IL-10) cytokines and chemokines (IL-8, IL-16) in preclinical development of type 1A diabetes mellitus (T1DM) in children.
Subjects and methods. An examination was made in 450 children who had normal blood glucose levels and a burdened history of positive or negative Langerhans islet autoantibodies (LIAA): IAA, GADA, and IA-2A over time until the clinical manifestations of DM1 emerged. The levels of the cytokines and chemokines were determined by ELISA and the titer of LIAA was by radioimmunoassay.
Results. Long before T1DM was clinically diagnosed, most children with normal blood glucose levels and LIAA had elevated levels of the cytokines IL-1α, IL-6, and α-TNF and the chemoattractants IL-8 and IL-16 with lower IL-4 concentrations as compared with the similar indices in children without LIAA and controls. After the disease manifested, the magnitude of changes in the indices under study reduced in the majority of children with LIAA, which may suggest that the autoimmune process subsides after destruction of most β-cells.
Conclusion. The elevated levels of IL-6, IL-16, α-TNF, and the chemokine IL-8 with the lower blood content of the cytokine IL-4 were long before the development of DM1 in children with normal blood glucose level in the presence of LIAA, which should be borne in mind while developing the immune mechanisms specifically directed against block, which participate by means of cytokines in β-cell destruction, as well as methods for preventing the development of T1DM in subjects with LIAA.

References

  1. Eisenbarth G. S. Update in type 1 diabetes. J. Clin. Endocrinol. 2007; 92 (7): 2403-2407.
  2. Pietropaolo M., Surhigh J. M., Nelson P. W., Eisenbarth G. S. Primer: immunity and autoimmunity. Diabetes 2008; 57: 2872-2882.
  3. Зак К. П., Малиновская Т. Н., Тронько Н. Д. Иммунитет у детей, больных сахарным диабетом. Киев: Книга плюс; 2002.
  4. Зак К. П., Попова В. В. Цитокины и сахарный диабет 1-го типа у человека (обзор с включением собственных данных). Укр. мед. часопис 2006; 1 (51): 78-88.
  5. Зак К. П., Попова В. В. Хемокины при сахарном диабете 1-го типа у человека. (Обзор литературы и собственные данные). Укр. мед. часопис 2008; 6 (68): 69-78.
  6. Röep B., Atkinson M. Animal model have little to teach us about type 1 diabetes. In support of this proposal. Diabetologia 2004; 47 (10): 1650-1656.
  7. Törn C., Mueller P. W., Bonifacio E. et al. Diabetes antibody standardization program: evaluation of assays for autoantibodies to glutamic acid decarboxylase and islet antigen-2. Diabetologia 2008; 51: 846-852.
  8. Попова В. В., Зак К. П. Открытие аутоантител к островкам Лангерганса поджелудочной железы - выдающееся достижение в области предсказания возникновения и диагностики типа сахарного диабета в клинике. (Обзор литературы). Лiкарська справа/Врач. дело 2006; 7: 3-12.
  9. Попова В. В. Частота виникнення цукрового дiабету 1 типу та iмунологiчний монiторинг у нормоглiкемiчних здорових дiтей з обтяженою спадковiстю i позитивних щодо дiабетасоцiйованих автоантитiл до острiвцiв Лангерганса. Ендокринологiя 2008; 13 (2): 211-219.
  10. Donath M. Y., Storling J., Berchtold L. A. et al. Cytokines and β-cell biology: from concept to clinical translation. Endocr. Rev. 2008; 29: 334-350.
  11. Hussain M. J., Maher J., Warnock T. et al. Cytokine overproduction in healthy first degree relative of patients with IDDM. Diabetologia 1998; 41:343-349.
  12. Kukreja A., Cost G., Marker J. Multiple immuno-regulatory defects in type-1 diabetes. J. Clin. Invest. 2002; 109 (1): 131-140.
  13. Hedman M., Ludvigsson J., Faresjo M. K. Nicotinamide reduces high secretion of IFN-gamma in high-risk relatives even though it does not prevent type 1 diabetes. J. Interferon Cytokine Res. 2006; 26 (4): 207-213.
  14. Basu S., Larsson A., Vessby J. et al. Type 1 diabetes is associated with increased cyclooxygenase- and cytokine-mediated inflammation. Diabet. Care 2005; 28: 1371-1375.
  15. Galassetti P. R., Iwanaga K., Crisostomo M. et al. Inflammatory cytokine, growth factor and counterregulatory responses to exercise in children with type 1 diabetes and healthy controls. Pediatr. Diabet. 2006; 7 (1): 16-24.
  16. Mysliwska J., Zorena K., Semetkowska-Jurkiewicz E. et al. High levels of circulating interleukin-10 in diabetic nephropathy patients. Eur. Cytokine Netw. 2005; 16 (2): 117-122.
  17. Gurgel-Convey E., Soura K. L. A., Eisner M., Lensen S. Effect of antiinflammatory cytokines on insulin-producing cells. Diabetologia 2004; 47 (Suppl. 1): 460.
  18. Avanzini M. A., Ciardelli L., Lenta E. et al. IFN-gamma low production capacity in type 1 diabetes mellitus patients at onset of disease. Exp. Clin. Endocrinol. Diabet. 2005; 113 (6): 313-317.
  19. Erbagci A. B., Tarakcioglu M., Coskun Y. et al. Mediators of inflammation in children with type 1 diabetes mellitus: cytokines in type 1 diabetic children. Clin. Biochem. 2001; 34 (8): 645-650.
  20. Lo H. C., Lin S. C., Wang Y. M. The relationship among serum cytokines, chemokine, nitric oxide, and leptin in children with type 1 diabetes mellitus. Clin. Biochem. 2004; 37 (8): 666-672.
  21. Попова В. В., Мельниченко С. В., Зак К. П. и др. О значительном снижении уровня хемокина ИЛ-16 в крови детей с впервые выявленным сахарным диабетом 1 типа. Лiкарська справа / Врач. дело 2004; 7: 32-34.
  22. Kolb H., Mandrup-Poulsen T. An immune origin of type 2 diabetes? Diabetologia 2005; 48 (6): 1038-1050.
  23. Baggiolini M. Chemokines in pathology and medicine. J. Intern. Med. 2001; 250: 9100-9104.
  24. Зак К. П., Грузов М. А., Афанасьева В. В. и др. Иммунитет в доклиническом периоде развития сахарного диабета 1-го типа у детей с отягощенной наследственностью и положительных к диабетассоциированным аутоантителам. Клин. мед. 2006; 8: 35-40.
  25. Popova V. V., Zak K. P., Gruzov M. A. et al. The prognostic value of immunological phenotype of lymphocytes in subjects positive for diabetes-associated autoantibodies. Diabetologia 2006; 49 (Suppl. 1): 280-281.

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) 2010 Consilium Medicum

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
 

Address of the Editorial Office:

  • Novij Zykovskij proezd, 3, 40, Moscow, 125167

Correspondence address:

  • Alabyan Street, 13/1, Moscow, 127055, Russian Federation

Managing Editor:

  • Tel.: +7 (926) 905-41-26
  • E-mail: e.gorbacheva@ter-arkhiv.ru

 

© 2018-2021 "Consilium Medicum" Publishing house


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies