Abstract
NONSPECIFIC IMMUNOLOGIC REACTIVITY IN RATS EXPOSED TO HYPOCALORIC DIET DURING PREGNANCY AND THEIR OFFSPRING
Sirenko V.A.
Inflammation as a manifestation of local tissue damage is a basis of a nonspecific component of the systemic immune response. Immune system mainly provides afferentation of information with cytokines which can be tracked to assess immune response. The study involved trials on 30 nonlinear pregnant rats (WAG/G Sto population) and their offspring. The levels of interleukin-4 (IL-4) and interleukin-12 (IL-12) in the blood serum were determined by immune-enzyme method using the sets of reactants of BEST Vector (Novosibirsk, the Russian Federation) and the sets of reactants of (Elisa Kit) Ani Biotech Oy, Orgenium laboratories Business Unit (Finland) according to the instructions attached.
Taking into consideration the disembodied data in the literature, dedicated to studying the issues, related to peculiarities of the immune system ontogenesis and orientation of immune responses, appearing secondary to pathological changes during perinatal and early periods of post-natal development, it is essential to clarify the role of the immune system in the mechanisms of damage of the pancreas structure and function. Assessment of the role of effector cytokines imbalance in immune reactions in rats exposed to hypocaloric diet during pregnancy and in their offspring, in comparison to the control, showed a significant imbalance of regulatory cytokines with a primary increase in IL-12 content, a decrease in IL-4 in rat mothers and 2-month-old infant rats, a decrease in both IL-12 content, and IL-4 in 1-month-old infant rats, demonstrating involvement in pathogenesis of damage of the pancreas and further development of chronic pancreatitis as both specific (Th-1) and nonspecific (macrophageal) cellular link of immunity. The latter is probably associated with an impairment of intercellular interaction, first of all, due to a decrease in functional activity of macrophages – cells of effectors, modulators of an immune response and sources of regulatory cytokines.
Keywords: hypocaloric diet, cytokines, nonspecific immunologic reactivity, pancreas.
СТАН НЕСПЕЦИФІЧНОЇ ІМУНОЛОГІЧНОЇ РЕАКТИВНОСТІ ЩУРІВ, ЯКІ ПЕРЕБУВАЛИ НА ГІПОКАЛОРІЙНІЙ ДІЄТІ ПІД ЧАС ВАГІТНОСТІ, ТА ЇХ ПОТОМСТВА
Сіренко В.А.
Запалення як прояв місцевого пошкодження тканин, є основою неспецифічної компоненти системної імунної відповіді. З боку імунної системи аферентація інформації здійснюється головним чином цитокінами, за допомогою яких можна простежити шлях реалізації імунної відповіді.
Обсяг дослідження включав експерименти на 30 нелінійних вагітних щурах (популяції WAG / G Sto) та їх потомстві. Рівні ІЛ-4 і ІЛ-12 в сироватці крові визначали імуноферментним методом за допомогою наборів реактивів фірми «Вектор Бест» (Новосибірськ, Росія) і наборів реактивів фірми (Elisa Kit) Ani Biotech Oy, Orgenium laboratories Business Unit (Finland) відповідно до доданих інструкцій. При з'ясуванні ролі дисбалансу ефекторних цитокінів крові в реалізації імунних реакцій щурів, що перебували на гипокалорийной дієті під час вагітності, та їх потомства в порівнянні з контролем, встановлено: наявність істотного дисбалансу регуляторних цитокінів з переважним збільшенням вмісту ІЛ-12, зниженням - ІЛ-4 у щурів - матерів і 2-х місячних щурят, зниження як змісту ІЛ-12, так і ІЛ-4 у 1-місячних щурят, що свідчить про залучення в патогенез ушкодження підшлункової залози і розвитку хронічного панкреатиту в подальшому, як специфічного (Тh 1) так і неспецифічного (макрофагального) клітинної ланки імунітету. Останнє, ймовірно, пов'язано з порушенням міжклітинної взаємодії за рахунок, в першу чергу, зниження функціональної активності макрофагів - клітин ефекторів, модуляторів імунної відповіді і джерел регуляторних цитокінів.
Ключові слова: гіпокалорійная дієта, неспецифічна імунологічна реактивність, цитокіни, підшлункова залоза.
СОСТОЯНИЙ НЕСПЕЦИФИЧЕСКОЙ ИММУНОЛОГИЧЕСКОЙ РЕАКТИВНОСТИ КРЫС, НАХОДИВШИХСЯ НА ГИПОКАЛОРИЙНОЙ ДИЕТЕ ВО ВРЕМЯ БЕРЕМЕННОСТИ, И ИХ ПОТОМСТВА
Сиренко В.А.
Воспаление как проявление местного повреждения тканей, является основой неспецифической компоненты системного иммунного ответа. Со стороны иммунной системы афферентация информации осуществляется главным образом цитокинами, с помощью которых можно проследить путь реализации иммунного ответа.
Объем исследования включал эксперименты на 30 нелинейных беременных крысах (популяции WAG / G Sto) и их потомстве. Уровни ИЛ-4 и ИЛ-12 в сыворотке крови определяли иммуноферментным методом с помощью наборов реактивов фирмы «Вектор Бест» (Новосибирск, Россия) и наборов реактивов фирмы (Elisa Kit) Ani Biotech Oy , Orgenium laboratories Business Unit (Finland) в соответствии с прилагаемыми инструкциями. При выяснении роли дисбаланса эффекторных цитокинов крови в реализации имунных реакций у находившихся на гипокалорийной диете во время беременности крыс и у их потомства, по сравнению с контролем, установлено: наличие существенного дисбаланса регуляторних цитокинов с преимущественным увеличением содержания ІЛ-12, снижением - ІЛ-4 у крыс - матерей и 2-х месячных крысят, снижение как содержания ІЛ-12, так и ІЛ-4 у 1- месячных крысят, что свидетельствует о вовлечении в патогенез повреждения поджелудочной железы и развития хронического панкреатита в дальнейшем, как специфического (Тh 1) так и неспецифического (макрофагального) клеточного звена иммунитета. Последнее, вероятно, связано с нарушением межклеточного взаимодействия за счет, в первую очередь, снижения функциональной активности макрофагов - клеток эффекторов, модуляторов иммунного ответа и источников регуляторных цитокинов.
Ключевые слова: гипокалорийная диета, неспецифическая иммунологическая реактивность, цитокины, поджелудочная железа.
Taking into consideration the disembodied data of the literature, dedicated to studying of the problems, connected with the peculiarities of the immune system ontogenesis and the orientation of immune responses, which arise against the background of pathological changes during perinatal and early periods of post-natal development of the organism, the clarification of the role of the immune system in the mechanisms of damage of the pancreas structure and function is important. At clarification of a role of the imbalance of effector cytokines in the blood in realization of immune reactions in the rats who were on a hypocaloric diet during their pregnancy and in their offsprings, in comparison with control, it is established: the existence of an essential imbalance of regulatory cytokines with primary increase of IL-12 content, decrease of IL-4 in rat mothers and 2-month-old infant rats, decrease of both IL-12 content, and IL-4 in 1-month-old infant rats that demonstrates involvement in a pathogenesis of damage of the pancreas and further development of chronic pancreatitis as both specific (Th 1) and nonspecific (macrophagic) cellular link of immunity. The latter is probably connected with the disturbance of intercellular interaction due to, first of all, decrease of functional activity of macrophages – cells of effectors, modulators of an immune response and sources of regulatory cytokines.
Keywords: hypocaloric diet, cytokines, nonspecific immunologic reactivity, pancreas.
References
Kazmirchuk, V.E., Koval'chuk, L.V., & Mal'cev, D.V. (2012). Klinicheskaya immunologiya i alergologiya s vozrastnymi osobennostyami: uchebnoye posobiye [Clinical immunology and allergology with age peculiarities: manual]. Kiev: Medicina
Glants, S. (1998). Mediko-b3olog3chna statystyka [Medical and biological statistics]. Moscow: Praktika
Jupp, J., Mansour, S., Johnson, C. D., Sanderson, J., Fine, D., & Gadola, S. (2015). T-cell populations in chronic pancreatitis. Pancreatology, 15, 4, 311-312. doi: 10.1016/j.pan.2015.04.009.
Talukdar, R., Sasikala, M., Pavan, K. P., Rao, G. V., Pradeep, R., & Reddy, D. N. (2016). T-Helper Cell-Mediated Islet Inflammation Contributes to β-Cell Dysfunction in Chronic Pancreatitis. Pancreas, 45, 3, 434-442. doi: 10.1097/MPA.0000000000000479.
Datsyuk, O.2. (2016). Discitok3nem3ya yak prediktor efektyvnosty startovoyi 3nfuz3ynoyi terap3yi v kompleks3 peredoperats3ynoyi p3dgotovky hvoryh na gostryi pankreatit [Disñitokinemia as a predictor of efficiency of starting infusional therapy in a complex of preoperative preparation of patients with acute pancreatitis]. Kl3n3chna h3rurg3ya, 5, 41–44.
Kuts, L.V. (2014). Kl3n3chna 3munolog3ya: pervynn3 3munodef3tsyty: navchalnyi pos3bnyk [Clinical immunology: primary immunodeficiencies: manual]. Sumy: SDU
Gregoriæ, P., Doklestiæ, K., Stankoviæ, S., Sijacki, A., Karamarkoviæ, A., Radenkoviæ, D., ... Bajec, D. (2014). Interleukin-12 as a predictor of outcome in patients with severe acute pancreatitis. Hepato-gastroenterology, 61, 129, 208–211.
Yang, W.-C., Hwang, Y.-S., Chen, Y.-Y., Liu, C.-L., Shen, C.-N., Hong, W.-H., ... Shen, C.-R. (2017). Interleukin-4 Supports the Suppressive Immune Responses Elicited by Regulatory T Cells. Frontiers in Immunology, 8, 1508. doi: 10.3389/fimmu.2017.01508
Zheng, H., Wei, F., Ma, X., Ban, Y., & Ma, X. (2016). Regulation of interleukin-12 production in antigen-presenting cells. Advances in Experimental Medicine and Biology, 941, 117-138. doi: 10.1007/ 978-94-024-0921-5_6
Zundler, S., & Neurath, M. F. (2015). Interleukin-12: Functional activities and implications for disease. Cytokine & Growth Factor Reviews, 26, 5, 559-568. doi: 10.1016/j.cytogfr.2015.07.003
"Inter Collegas" is an open access journal: all articles are published in open access without an embargo period, under the terms of the CC BY-NC-SA (Creative Commons Attribution ‒ Noncommercial ‒ Share Alike) license; the content is available to all readers without registration from the moment of its publication. Electronic copies of the archive of journals are placed in the repositories of the KhNMU and V.I. Vernadsky National Library of Ukraine.
Copyright Agreement
1. This Agreement on the transfer of rights to use the work from the Co-authors to the publisher (hereinafter the Agreement) is concluded between all the Co-authors of the work, represented by the Corresponding Author, and Kharkiv National Medical University (hereinafter the University), represented by an authorized representative of the Editorial Board of scientific journals (hereinafter the Editorial Board).
2. This Agreement is an accession agreement within the meaning of clause 1 of Article 634 of the Civil Code of Ukraine: that is, a contract, "the terms of which are established by one of the parties in forms or other standard forms, which can be concluded only by joining the other party to the proposed contract as a whole. The other party cannot offer its terms of the contract." The party that established the terms of this contract is the University.
3. If there is more than one author, the authors choose the Corresponding Author, who communicates with the Editorial Board on his own behalf and on behalf of all Co-authors regarding the publication of a written work of a scientific nature (article or review, hereinafter referred to as the Work).
4. The contract begins from the moment of submission of the manuscript of the Work by the Corresponding Author to the Editorial Board, which confirms the following:
4.1. all Co-authors of the Work are familiar with and agree with its content, at all stages of reviewing and editing the manuscript and the existence of the published Work;
4.2. all Co-authors of the Work are familiar with and agree to the terms of this Agreement.
5. The published Work is in electronic form in public access on the websites of the University and any websites and electronic databases in which the Work is posted by the University and is available to readers under the terms of the "Creative Commons" license (Attribution NonCommercial Sharealike 4.0 International)" or more free licenses "Creative Commons 4.0".
6. The Corresponding Author transfers, and the University receives, the non-exclusive property right to use the Work by placing the latter on the University's websites for the entire term of copyright. The University participates in the creation of the final version of the Work by reviewing and editing the manuscript of the article or review provided to the Editorial Board by the Corresponding Author, translating the Work into any languages. For the participation of the University in the finalization of the Work, the Co-authors agree to pay the invoice issued to them by the University, if such payment is provided by the University. The size and procedure of such payment are not the subject of this contract.
7. The University has the right to reproduce the Work or its parts in electronic and printed forms, to make copies, permanent archival storage of the Work, distribution of the Work on the Internet, repositories, scientometric databases, commercial networks, including for monetary compensation from third parties.
8. The co-authors guarantee that the manuscript of the Work does not use works whose copyright belongs to third parties.
9. The authors of the Work guarantee that at the time of submission of the manuscript of the Work to the Editorial Board, the property rights to the Work belong only to them, neither in whole nor in part have they been transferred to anyone (not alienated), they are not the subject of a lien, litigation or claims by third parties.
10. The Work may not be posted on the University's website if it violates a person's right to the privacy of his personal and family life, harms public order and health.
11. The work may be withdrawn by the Editorial Board from the University websites, libraries and electronic databases where it was placed by the Editorial Board, in cases of detection of violations of the ethics of the authors and researchers, without any compensation for the losses of the Co-authors. At the time of submission of the manuscript to the Editorial Board and all stages of its editing and review, the manuscript must not have already been published or submitted to other editorial offices.
12. The right transferred under this Agreement extends to the territory of Ukraine and foreign countries.
13. The rights of Co-authors include the requirement to indicate their names on all copies of the Work or during any public use or public mention of the Work; the requirement to preserve the integrity of the Work; legal opposition to any distortion or other encroachment on the Work, which may harm the honor and reputation of the Co-authors.
14. Co-authors have the right to control their personal non-property rights by familiarizing themselves with the text (content) and form of the Work before its publication on the University's website, when transferring it to a printing company for reproduction or when using the Work in other ways.
15. The Co-authors, in addition to the property rights not transferred under this Agreement and taking into account the non-exclusive nature of the rights transferred under this Agreement, retain the property rights to finalize the Work and to use certain parts of the Work in other works created by the Co-authors.
16. The Co-authors are obliged to notify the Editorial Board of all errors in the Work, discovered by them independently after the publication of the Work, and to take all measures to eliminate such errors as soon as possible.
17. The University undertakes to indicate the names of the Co-authors on all copies of the Work during any public use of the Work. The list of Co-authors may be shortened according to the rules for the formation of bibliographic descriptions determined by the University or third parties.
18. The University undertakes not to violate the integrity of the Work, to agree with the Corresponding Author on all changes made to the Work during processing and editing.
19. In case of violation of their obligations under this Agreement, its parties bear the responsibility defined by this Agreement and the current legislation of Ukraine. All disputes under the Agreement are resolved through negotiations, and if the negotiations do not resolve the dispute – in the courts of the city of Kharkiv.
20. The parties are not responsible for the violation of their obligations under this Agreement, if it occurred through no fault of theirs. The party is considered innocent if it proves that it has taken all measures dependent on it for the proper fulfillment of the obligation.
21. The Co-authors are responsible for the truthfulness of the facts, quotes, references to legislative and regulatory acts, other official documentation, the scientific validity of the Work, all types of responsibility to third parties who have claimed their rights to the Work. The co-authors reimburse the University for all costs caused by claims of third parties for infringement of copyright and other rights to the Work, as well as additional material costs related to the elimination of identified defects.