Pathogenetic rationale for usage of recombinant interleukins in the patients with mandibular fractures to prevent post-traumatic osteomyelitis

Cover Page

Cite item

Abstract

The paper presents the results on spontaneous and induced production of IFNγ, IL-4, IL-13 cytokines in blood cells of patients with mandibular fractures and post-traumatic osteomyelitis. Osteomyelitis of the jaw represents one of the urgent challenges in modern medicine. There are many reasons for development of purulent necrotic processes of the jaw bones, including disorders of innate and adaptive immune response. Currently, the immunological aspects of post-traumatic complications of maxillofacial region remain poorly understood. There are no unambiguous and systematic studies of immune mechanisms in pathogenesis of post-traumatic osteomyelitis of the lower jaw. The aim of our study was to theoretically confirm application of recombinant interleukins (IL-1β, IL-2, IFNγ) in the patients with jaw fractures, in order to prevent osteomyelitis, as based on the studies of spontaneous and induced cytokine production (IFNγ, IL-4, IL-13). Spontaneous and stimulated production of IFNγ, IL-4, and IL-13 cytokines by blood cells was determined using specific reagent kits from R&D Diagnostic Inc. (USA). The results were recorded using an ELISA Multiscan analyzer (Finland). Statistical significance of intergroup differences was determined by the Mann–Whitney method. The level of statistical significance at which the null hypotheses were rejected was < 0.05. To stratify the cases of post-traumatic osteomyelitis and uncomplicated mandibular fracture, the models were developed with a singlelayer neural network, using the nnet R-studio package. To assess quality of the models, the areas under the ROC curves (AUC), Akaike criterion (AIC), and the relative classification accuracy (OTC) were used, which was determined as the ratio of correctly established model diagnosis numbers to the total number of patients. The study results demonstrate that the patients with mandibular fractures exhibit a moderate impairment of LPS-induced IL-4 and IFNγ production by leukocytes with IL-13 activation. In presence of osteomyelitis, this imbalance is promoted, thus suggesting an impaired ability of the cells to produce IL-4 and IFNγ. An opportunity for usage immunomodulation when treating the patients with mandibular fractures is represented by P = 1/(1+e-z) where z is defined via IL-1β, IL-2 and IFNγ levels on the first day of observation. In vitro supplementation with recombinant IL-1β and IFNγ modulates cell function, improving the cytokine profile. The prognostic models, imitating binary logistic regression, were used to demonstrate that recombinant IL-1β could be used to prevent patients with mandibular fractures from developing post-traumatic osteomyelitis (AIC = 13.2, AUC = 0.96, р = 0.026).

About the authors

E. V. Paskova

Pacific State Medical University

Author for correspondence.
Email: popovavl@list.ru

Paskova Elena V.., PhD (Medicine), Assistant Professor, Department of Normal and Pathological Physiology

690002, Vladivostok, Ostryakov ave., 4

Russian Federation

E. V. Markelova

Pacific State Medical University

Email: fake@neicon.ru

PhD, MD (Medicine), Рrofessor, Head, Department of Normal and Pathological Physiology

Vladivostok

A. A. Golitsyna

Pacific State Medical University

Email: fake@neicon.ru

Postgraduate Student

Vladivostok

E. Yu. Rusakova

Far Eastern Federal University

Email: fake@neicon.ru

PhD, MD (Medicine), Рrofessor, School of Biomedicine

Vladivostok

A. L. Romanchuk

Pacific State Medical University

Email: fake@neicon.ru

Postgraduate Student

Vladivostok

D. A. Nevezhkin

Pacific State Medical University

Email: fake@neicon.ru

Postgraduate Student

Vladivostok

S. V. Knysh

Pacific State Medical University

Email: fake@neicon.ru

PhD (Medicine), Assistant Professor, Department of Normal and Pathological Physiology

Vladivostok

References

  1. Кирпичников М.В., Подольский В.В. К вопросу об этиологических факторах травматического остеомиелита нижней челюсти // Актуальные вопросы стоматологии, 2017. С. 172-176.
  2. Кулигин Д.А. Этиологические факторы травматического остеомиелита // Бюллетень медицинских Интернет-конференций, 2017. Т. 7, № 10. С. 1536-1537.
  3. Латюшина Л.С., Бережная Е.С., Долгушин И.И., Финадеев А.П., Павлиенко Ю.В. Влияние иммунотерапии рекомбинантным IL-1β на клинико-иммунологические показатели пациентов с осложненными переломами нижней челюсти // Проблемы стоматологии, 2017. Т. 13, № 2. С. 49-53.
  4. Малютина А.В., Николаева Б.В., Пинелис И.С., Турчина Е.В. Причинно-следственные связи развития травматического остеомиелита челюстей // Медицина завтрашнего дня: материалы XVI Межрегиональной научно-практической конференции студентов и молодых ученых: сб. научных трудов: электронный ресурс. Редакционно-издательский центр Читинской государственной медицинской академии, 2017. С. 137-138.
  5. Матчин А.А., Абдуллаев М.Д., Ахмерова Р.И., Рахматуллин Т.Р. Клинический анализ иммунологических факторов риска развития воспалительно-деструктивного процесса в костях лицевого скелета // Современные медицинские исследования: сб. статей XVIII Международной научной медицинской конференции, г. Кемерово, 19 марта 2018 г. / Отв. ред. П.И. Никитин. Кемерово: Плутон, 2018. С. 27-29.
  6. Симбирцев А.С. Цитокины в патогенезе и лечении заболеваний человека. СПб: Фолиант, 2018. 512 с.
  7. Delsing C.E., Becker K.L., Simon A., Kullberg B.J., Bleeker-Rovers C.P., van de Veerdonk F.L., Netea M.G. Th17 cytokine deficiency in patients with Aspergillus skull base osteomyelitis. BMC Infect. Dis., 2015, Vol. 15, 140. doi: 10.1186/s12879-015-0891-2.
  8. Kim S.M., Eo M.Y., Cho Y.J. Immunoprecipitation high performance liquid chromatographic analysis of healing process in chronic suppurative osteomyelitis of the jaw. J. Craniomaxillofac. Surg., 2018, Vol. 46, no. 1, pp. 119-127.
  9. Kharazmi M., Hallberg P. Mucosal trauma and osteonecrosis. Am. J. Orthod. Dentofacial Orthop., 2018, Vol. 154, no. 2, p. 155.
  10. Morita M., Iwasaki R., Sato Y. Elevation of pro-inflammatory cytokine levels following antiresorptive drug treatment is required for osteonecrosis development in infectious osteomyelitis. Sci. Rep., 2017, Vol. 7, 46322. doi: 10.1038/srep46322.

Supplementary files

There are no supplementary files to display.


Copyright (c) 2021 Paskova E.V., Markelova E.V., Golitsyna A.A., Rusakova E.Y., Romanchuk A.L., Nevezhkin D.A., Knysh S.V.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Свидетельство о регистрации СМИ ПИ № 77 - 11525 от 04.01.2002 выдано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).


This website uses cookies

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

About Cookies