THE LEVEL OF PROINFLAMATORY CYTOKINES IN CELLS CULTURES SUPERNATANTS IN CHILDREN WITH JUVENILE IDIOPATHIC ARTHRITIS
DOI: 10.22138/2500-0918-2018-15-3-421-431
I.M. Krivolapova, I.A. Pashnina, V.A. Chereshnev
Regional Children's Clinical Hospital №1, Yekaterinburg, Russian Federation;
Institute of Immunology and Physiology Urals Branch of the Russian Academy of Sciences, Yekaterinburg, Russian Federation
Abstract. Juvenile idiopathic arthritis is a chronic inflammatory disease of joints in children. Hyperproduction of proinflammatory cytokines, in particular, plays the role in pathogenesis of juvenile idiopathic arthritis. The aim — to determine spontaneous and stimulated proinflammatory cytokines production by peripheral blood cells in children with juvenile idiopathic arthritis. Materials and methods. Patients of 2–17 years old with different subtypes of juvenile idiopathic arthritis (n = 100) and healthy children without signs of autoimmune diseases (control, n = 31) were examined. Spontaneous and PHA-stimulated concentrations of IL-1?, IL-6, IL-8, IFN?, TNF? in the cells cultures supernatants were determined by ELISA. The results. Differences in the spontaneous and stimulated production of the investigated cytokines in patients with different subtypes of juvenile arthritis were not revealed. Increasing of spontaneous production by blood cells of IL-1?, IL-8, TNF-? and IFN? was found in the combined group of patients with arthritis in comparison with healthy children. Stimulated IL-6 and TNF-? production was increased in patients with juvenile idiopathic arthritis, whereas stimulated IL-1?, IL-8, IFN? production was decreased in comparison with the control. Conclusion. Increase spontaneous production of cytokines in children with juvenile idiopathic arthritis indicates a previous activation of immunocompetent cells in patients. High spontaneous and/or stimulated IL-1?, IL-6, IL-8, TNF-?, IFN? production by blood cells in patients reflects the pathogenic significance of these cytokines in disease. Decrease of stimulated IL-1?, IL-8, IFN? production in patients with juvenile idiopathic arthritis in comparison with the control is an evidence of immunocompetent cells functional reserve decline.
Keywords: cytokines, juvenile idiopathic arthritis
Received 28.12.2017
For citation:
Krivolapova I.M., Pashnina I.A., Chereshnev V.A. The level of proinflamatory cytokines in cells cultures supernatants in children with juvenile idiopathic arthritis. Vestn. Ural. Med. Akad. Nauki. = Journal of Ural Medical Academic Science. 2018, Vol. 15, no. 3, pp. 421–431. DOI: 10.22138/2500-0918-2018-15-3-421-431 (In Russ)
REFERENCES
1. Alekseeva Ye.I., Bzarova T.M. Juvenile idiopathic arthritis. In the book: Pediatrics. National guidance. Short edition [V kn.: A.A. Baranova Pediatriya. Nacional'noe rukovodstvo. Kratkoe izdanie.]. Moskva: GEOTAR-Media. 2014: 768 p. (In Russ.).
2. Huang J.L. New Advances in Juvenile Idiopathic Arthritis. Chang Gung Med J. 2012. Vol. 35, pp. 1-14.
3. Alekseeva Ye.I. Juvenile idiopathic arthritis: Clinical picture, Diagnosis, Treatment. Current Pediatrics = Voprosy sovremennoj pediatrii. 2015, no. 14 (1), pp. 78-94. (In Russ.).
4. Correll C.K., Binstadt B.A. Advances in the pathogenesis and treatment of systemic juvenile idiopathic arthritis. Pediatric Research. 2014. Vol. 75, pp. 176–183. DOI: 10.1038/pr2013.187.
5. Ketlinsky S.A., Simbircev A.S. Cytokines. Sankt-Peterburg: Foliant. 2008. 552 p. (In Russ.).
6. Y?lmaz M., Kendirli, S.G., Alt?ntas D., Bing G., Antmen B. Cytokine levels in serum of patients with juvenile rheumatoid arthritis. Clinical Rheumatology. 2001. Vol. 20 (1), pp. 30-35.
7. Szymanska-Kaluza J., Cebula-Obrzut B., Smolewski P., Stanczyk J., Smolewska E. Imbalance of Th17 and T-regulatory cells in peripheral blood and synovial fluid in treatment naive children with juvenile idiopathic arthritis. Central European Journal of Immunology. 2014. Vol. 39 (1), pp. 71-76. DOI: 10.5114/ceji.2014.42128.
8. Dem'yanov A.V., Kotov A.YU., Simbircev A.S. Diagnostic value of cytokine studies in clinical practice. Cytokines and inflammation = Citokiny i vospalenie. 2003, no. 2 (3), pp. 20-35. (In Russ.).
9. Gorska A., Kowal-Bielecka O., Urban M., Pietrewicz E. Interleukin-6 and tumor necrosis factor alpha levels in the serum and synovial fluid in relation to bone mineral density and turnover in children with juvenile idiopathic arthritis. Clinical immunology Centr. Eur. J. Immunol. 2008. Vol. 33 (4), pp. 216-219.
10. Pietrewicz E., Urban M., Gorska A. Cytokine levels in serum of patients with juvenile idiopathic arthritis depending on subtype and disease activity. Pol. Merkur. Lekarski. 2004. Vol. 17 (99), pp. 232-234.
11. Fedorov E.S., Salugina S.O., Kuz'mina N.N. The role of cytokine network in the regulation of inflammation in different subtype of juvenile arthritis. Rheumatology Science and Practice = Nauchno-prakticheskaya revmatologiya. 2009, no. 3, pp. 74-89. (In Russ.).
12. De Benedetti F., Pignatti P., Bernasconi S., Gerloni V., Matsushima K., Caporali R., et al. Interleukin 8 and monocyte chemoattractant protein-1 in patients with juvenile rheumatoid arthritis. Relation to onset types, disease activity, and synovial fluid leukocytes. J. Rheumatol. 1999. Vol. 26 (2), pp. 425-431.
13. Sebbag M., Parry S.L., Brennan F.M., Feldmann M. Cytokine stimulation of T lymphocytes regulates their capacity to induce monocyte production of tumor necrosis factor-alpha, but not interleukin-10: possible relevance to pathophysiology of rheumatoid arthritis. Eur. J. Immunol. 1997. Vol. 27 (3), pp. 624-632. DOI: 10.1002/eji.1830270308.
14. Moller B., Paulukat J., Nold M., Behrens M., Kukoc-Zivojnov N., Kaltwasser J. P. et al. Interferon-? induces expression of interleukin-18 binding protein in fibroblast-like synoviocytes. Rheumatology. 2003. Vol. 42 (3), pp. 442–445. DOI: 10.1093/rheumatology/keg146.
15. Muller K., Herner E.B., Stagg A., Bendtzen K., Woo P. Inflammatory cytokines and cytokine antagonists in whole blood cultures of patients with systemic juvenile chronic arthritis. Br. J. Rheumatol. 1998. Vol. 37 (5), pp. 562-569.
16. Novikov A.A., Aleksandrova E.N., Diatroptova M.A., Nasonov E.L. The role of cytokines in pathogenesis of rheumatoid arthritis. Rheumatology Science and Practice =Nauchno-prakticheskaya revmatologiya. 2010, no. 2, pp. 71-82. (In Russ.).
17. Aggarwal А., Mishra R. Cytokine production by peripheral blood mononuclear cells patients with juvenile idiopathic arthritis. Indian Pediatrics. 2002. Vol. 3, pp. 739-742.
18. Heney D., Whicher T.J. Factors affecting the measurement of cytokines in biological fluids: implications for their clinical measurement. Ann. Clin. Biochem. 1995. Vol. 32, pp. 358-368.
19. Konenkov V.I., Rakova I.G., Avdoshina V.V., Gel'fgat E.L. Complex evaluation of spontaneous cytokines production in the culture of peripheral blood mononuclear cells of healthy person. Cytokines and inflammation = Citokiny i vospalenie. 2005, no. 2, pp. 33-37. (In Russ.).
20. Gusev E.Yu., Chereshnev V.A., Zhuravleva Yu.A., Solomatina L.V., Zubova T.Eh. The variants of chronic systemic inflammation development. Medical immunology = Meditsinskaya immunologiya. 2009, no. 4 (2-3), pp. 131-140. (In Russ.).
21. Gajdash E.I., Gajdash I.S., Dychko E.A., Kohan S.T. Pokazateli sekretornoj aktivnosti nejtrofilov i monocitov krovi cheloveka pod vliyaniem lipopolisaharidov bakterij roda Shigella in vitro. Zdorov'e dlya vsekh. 2013, no. 2, pp. 3-6. (In Russ.).
22. Pascual V., Allantaz F., Arce E., Purano M., Role of interleukin-1(IL-1) in the pathogenesis in systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade. J. Exp. Med. 2005. Vol. 201, pp. 1479-1486. DOI: 10.1084/jem.20050473.
23. Raziuddin S., Bahabri S., Al-Dalaan., Siraj A.K., Al-Sedairy S. A mixed Th1/Th2 cell cytokine response predominantes in systemic onset juvenile rheumatoid arthritis: immunoregulatory IL-10 function. Clin. Immunol. Immunopatol. 1998. Vol. 86, pp. 192-198.
24. Pignatti P., Vivarelli M., Meazza C., Rizzolo M.G., Martini A., De Benedetti F. Abnormal regulation of interleukin 6 in systemic juvenile idiopathic arthritis. J. Rheumatol. 2001. Vol. 28 (7), pp. 1670-1676.
25. Zlakomanova O.N. System of cytokine in children with traumatic. Traumatology and Orthopaedics of Russia = Travmatologiya i ortopediya Rossii. 2008, no. 2 (48), pp. 65-71. (In Russ.).
26. Katial R.K., Sachanandani D., Lieberman M.M. Cytokine Production in cell culture by peripheral blood mononuclear cells from immunocompetent hosts. Clin. Diagn. Lab. Immunol. 1998. Vol. 5 (1), pp. 78–81.
27. Poveshchenko O.V., Kim I.I., Shevchenko A.V., Pokushalov Ye.A., Romanov A.B., Bondarenko N.A. i dr. Evaluation of level of cytokines produced by peripheral blood mononuclear cells of patients with chronic heart failure after mobilization of bone marrow stem cells with G-CSF. The Bulletin of Siberian Branch of Russian Academy of Russian Academy of Medical = Byulleten' SO RAMN. 2014, no. 34 (4), pp. 42-47. (In Russ.).
28. Cannon G.W., Pincus S.H., Emkey R.D., Denes A., Cohen S.A., Wolfe F. et al Double-blind trial of recombinant ?-interferon versus placebo in the treatment of rheumatoid arthritis. Arthritis and Rheumatism. 1989. Vol. 32 (8), pp. 964-973.
29. Pashnina I. A. Spontaneous and phytogemagglutinin-stimulated expression of actovation markers CD25, CD38, CD69 on T-lymphocytes in children with different pathology. Russian journal of immunology = Rossijskij immunologicheskij zhurnal. 2017, no. 11 (20) (3), pp. 465-467. (In Russ.).
Authors
Irina M. Krivolapova
Regional Children's Clinical Hospital №1, Clinical Diagnostic Laboratory
Biologist
S. Deryabina str., 32, Yekaterinburg, Russian Federation, 620149
krivolapovaim@mis66.ru
Irina A. Pashnina
Regional Children's Clinical Hospital №1, Clinical and diagnostic laboratory
Dr. Sci. (Bio.), Head of the laboratory
S. Deryabina str., 32, Yekaterinburg, Russian Federation, 620149
irina_pashnina@list.ru
Valeriy А. Chereshnev
Institute of Immunology and Physiology, Urals Branch of the Russian Academy of Sciences Academician of the Russian Academy of Sciences, Dr. Sci. (Med.), Professor
Pervomayskaya str., 106, Yekaterinburg, Russian Federation, 620049
iip@iip.uran.ru