Hormone therapy affecting interferon defense in children with infectious mononucleosis

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Abstract

23 children diagnosed with acute infectious mononucleosis were hospitalized and examined after a short prednisolone treatment course. Related interferon status during infection was compared with that in 38 patients with acute infectious mononucleosis receiving no hormone therapy. Interferon status was investigated by Ershov method, allowing to estimate amount of interferon in the blood serum samples or patient blood cell culture by assessing interferon biological activity. Along with measuring IFNα or IFNγ biological activity, their level was quantified by using enzyme immunoassay. Immunological examination conducted on the next day after the end of hormone therapy revealed sharply decreased potential of patient blood cells to produce both IFNα and IFNγ. The multiplicity of IFNα and IFNγ titer reduction in various patients varied by 4–5 and 3–4-fold, respectively. The concentration of IFNα, determined by ELISA, decreased by 4–6-fold, whereas for IFNγ — by 1.5–2-fold. A follow-up examination 1 month after discharge from the clinic showed that mean IFNα titer in children aged 3–6 years and treated with prednisolone was significantly reduced compared to the baseline, whereas most patients receiving no hormone therapy had normal IFNα production. The change in the level of IFNα 1 month after hormone therapy in 7–14-year age group was similar. IFNγ production quickly recovered, and 1 month after discharge from the clinic, its concentration in culture supernatants from patients reached 10–15 ng/ml, exceeding normal values more than twice. The biological activity of IFNγ in these culture supernatants was significantly higher than those immediately after hormone therapy, whereas in 3–6-year-old group of patients it was also higher than baseline level. These results can serve as a laboratory justification for including recombinant IFNα-2b drugs in the therapy of such patients, presumably immediately after the end of hormone course. Overall, laboratory justified administration of interferon preparations seems to be necessary to determine optimal timepoint for applying such drugs to increase effectiveness for achieving a durable patient recovery.

About the authors

I. M. Fedorova

G.N. Gabrichevsky Moscow Research Institute of Epidemiology and Microbiology

Author for correspondence.
Email: vestnik-07@mail.ru
ORCID iD: 0000-0002-0335-2752

Irina M. Fedorova,  PhD (Medicine), Leading Researcher, Laboratory for the Study of Cellular and Molecular Bases of Immunity 

125212, Moscow, Admiral Makarov str., 10

Phone: +7 903 107-60-67. Fax: +7 (495) 452-18-30

Russian Federation

S. I. Koteleva

G.N. Gabrichevsky Moscow Research Institute of Epidemiology and Microbiology

Email: felileo@yandex.ru
ORCID iD: 0000-0003-1878-2234

PhD (Medicine), Leading Researcher, Laboratory for the Study of Cellular and Molecular Bases of Immunity 

Moscow

Russian Federation

I. V. Kapustin

G.N. Gabrichevsky Moscow Research Institute of Epidemiology and Microbiology

Email: vano-kapusta@inbox.ru
ORCID iD: 0000-0001-6191-260X

PhD (Medicine), Leading Researcher, Laboratory for the Study of Cellular and Molecular Bases of Immunity 

Moscow

Russian Federation

M. S. Blyakher

G.N. Gabrichevsky Moscow Research Institute of Epidemiology and Microbiology

Email: msb2222@list.ru
ORCID iD: 0000-0003-3480-6873

PhD, MD (Medicine), Professor, Head of the Laboratory for the Study of Cellular and Molecular Bases of Immunity 

Moscow

Russian Federation

E. A. Tulskaya

G.N. Gabrichevsky Moscow Research Institute of Epidemiology and Microbiology

Email: etul@mail.ru
ORCID iD: 0000-0003-1969-4009

PhD (Biology), Senior Researcher, Laboratory for the Study of Cellular and Molecular Bases of Immunity 

Moscow

Russian Federation

N. N. Zvereva

Pirogov Russian National Research Medical University

Email: zvereva_nadezhda@mail.ru
ORCID iD: 0000-0003-2699-0439

PhD (Medicine), Associate Professor, Department of Infectious Diseases in Children 

Moscow

Russian Federation

M. A. Ilina

Pirogov Russian National Research Medical University

Email: ilina_mar@list.ru
ORCID iD: 0000-0003-4227-5363

Pediatrician, Department of Infectious Diseases in Children 

Moscow

Russian Federation

M. A. Saifullin

Infectious Hospital No. 1

Email: dr_saifullin@mail.ru
ORCID iD: 0000-0003-1058-3193

PhD (Medicine), Associate Professor, Department of Infectious Diseases in Children 

Moscow

Russian Federation

A. A. Samkov

Infectious Hospital No. 1

Email: alex-ridiger@mail.ru

Infectiologist, Pediatrician, Head of the Department No. 13 

Moscow

Russian Federation

E. V. Vlasov

Infectious Hospital No. 1

Email: ikb1@zdrav.mos.ru

Infectiologist, Pediatrician, Deputy Head Physician of the Department No. 13 

Moscow

Russian Federation

References

  1. Барычева Л.Ю., Голубева М.В., Волкова А.В. Показатели адаптивного иммунитета у детей с инфекционным мононуклеозом, обусловленным вирусом Эпштейна–Барр // Кубанский научный медицинский вестник. 2012. № 2 (131). С. 30–33. [Barycheva L.U., Golubeva M.V., Volkova A.V. Indicators of adaptive immunity for children with infectious mononucleosis conditioned with the virus of Epstein–Barr. Kubanskiy nauchnyy meditsinskiy vestnik = Kuban Scientific Medical Bulletin, 2012, no. 2 (131), pp. 30–33. (In Russ.)]
  2. Дрыганова М.Б., Мартынова Г.П., Куртасова Л.Б. Характеристика острого периода инфекционного мононуклеоза Эпштейна–Барр-вирусной этиологии у детей в зависимости от индивидуальной клеточной чувствительности к интерферону α-2 // Детские инфекции. 2011. № 3. С. 15–17. [Dryganova M.B., Martynova G.P., Kurtasova L.M. Features of acute period of infectious mononucleosis of Epstein–Barr virus etiology in children depending on individual cell sensitivity to interferon α-2. Detskie infektsii = Children’s Infections, 2011, no. 3, pp. 15–17. (In Russ.)]
  3. Клинические рекомендации (протокол лечения) оказания медицинской помощи детям, больным инфекционным мононуклеозом. Утверждено на заседании Профильной комиссии ФГБУ НИИДИ ФМБА России 9 октября 2013 г. (код протокола 91500.11.В27.001.2013). [Clinical recommendation (treatment protocol) of medical aid to children with infectious mononucleosis. Approved at the meeting of the Profile Commission of Research Institute of Children’s Infections FMBA of Russia (protocol code 91500.11.В27.001.2013). (In Russ.)] URL: http://niidi.ru/dotAsset/a6816d03-b0d9-4d37-9b09-540f48e3ed43.pdf
  4. Крамарь Л.В., Карпухина О.А. Комплексная терапия Эпштейна–Барр-вирусной инфекции у детей // Архив внутренней медицины. 2012. № 1 (3). С. 25–29. [Kramar L.V., Karpukhina O.A. Complex therapy of Epstein–Barr viral infection in children. Arkhiv vnutrennei meditsiny = Archive of Internal Medicine, 2012, no. 1 (3), pp. 25–29. (In Russ.)]
  5. Кудин А.П. Некоторые вопросы терапии инфекционного мононуклеоза у детей // Медицинский журнал. 2012. № 3. С. 138–143. [Kudin A.P. Some questions of therapy infectious mononucleosis at children. Meditsinskii zhurnal = Medical Journal, 2012, no. 3, pp. 138–143. (In Russ.)]
  6. Курмаева Д.Ю., Баранова И.П. Терапевтическая эффективность различных форм циклоферона при лечении инфекционного мононуклеоза у детей // Антибиотики и химиотерапия. 2011. Т. 56, № 9–10. С. 33–36. [Kurmaeva D.Yu., Baranova I.P. Therapeutic efficacy of various formulations in the treatment of infectious mononucleosis in children. Antibiotiki i khimioterapiya = Antibiotics and Chemotherapy, 2011, vol. 56, no. 9–10, pp. 33–36. (In Russ.)]
  7. Куртасова Л.М., Шакина Н.А., Шмидт А.Р. Клеточная чувствительность к интерферону-α2 in vitro у детей с инфекционным мононкулеозом, вызванным вирусом Эпштейна–Барр // Медицинская иммунология. 2016. Т. 18, № 1. С. 79–84. [Kurtasova L.M., Shakina N.A., Schmidt A.R. In vitro cellular response to interferon-α2 in children with infectious mononucleosis caused by Epstein–Barr virus. Meditsinskaya immunologiya = Medical Immunology (Russia), 2016, vol. 18, no. 1, pp. 79–84. (In Russ.)] doi: 10.15789/1563-0625-2016-1-79-84
  8. Левина А.С., Железникова Г.Ф., Иванова В.В., Бабаченко И.В., Монахова Н.Н., Комелева Е.В., Мурина Е.А. Эффективность иммунокорригирующей терапии при инфекционным мононуклеозе у детей // Детские инфекции. 2009. № 1. С. 60–63. [Levina A.S., Zheleznikova G.F., Ivanova V.V., Babachenko I.V., Monakhova N.E., Komeleva E.V., Murina E.A. Effectiveness of immunocorrective therapy at infectious mononucleosis in children. Detskie infektsii = Children’s Infections, 2009, no. 1, pp. 60–63. (In Russ.)]
  9. Определение интерферонового статуса как показателя неспецифической резистентности организма человека. Практические рекомендации ассоциации специалистов и организаций лабораторной службы «Федерация лабораторной медицины». Под ред. Ф.И. Ершова. Москва: 2018. 26 с. [Determination of interferon status, as an indicator of non-specific resistance of the human body. Practical recommendations of the Association of Laboratory Specialists and Organizations “Federation of Laboratory Medicine”. Ed. by F.I. Ershov. Moscow: 2018. 26 p. (In Russ.)]
  10. Подчерняева Н.С. Глюкокортикоиды в детской ревматологии: status praesans // Педиатрия. 2016. Т. 95, № 4. С. 150–159. [Podchernyaeva N.S. Glucocorticoids in pediatric rheumatology: status praesans. Pediatriya = Pediatrics, 2016, vol. 95, no. 4, pp. 150–159. (In Russ.)]
  11. Притулина Ю.Г., Кунина В.В., Монастырский А.А., Малюткина Т.Н., Малиновская В.В., Шувалов А.Н. Новые подходы к терапии инфекционного мононуклеоза // Лечащий врач. 2019. № 9. С. 57–59. [Pritulina Yu.G., Kunina V.V., Monastyrsky A.A., Malyutkina T.N., Malinovskaya V.V., Shuvalov A.N. New approaches to the therapy of infectious mononucleosis. Lechaschii vrach = The Attending Physician, 2019, no. 9, pp. 57–59. (In Russ.)] doi: 10.26295/OS.2019.80.68.012
  12. Тодосенко Н.М., Хазиахматова О.Г., Юрова К.А., Малинина И.П., Литвинова Л.С. Влияние метилпреднизолона на процессы активации CD4+CD45RO+ Т-клеток при ревматоидном артрите (in vitro) // Цитология. 2017. Т. 59, № 6. С. 421–427. [Todosenko N.M., Khaziakhmatova O.G., Yurova K.A., Litvinova L.S., Malinina I.P. Influence of methylprednisolone in vitro during activation of CD4+CD45RO+ T-cells in norm and chronic rheumatoid arthritis. Tsitologiia = Cell and Tissue Biology, 2017, vol. 11, no. 6, pp. 427–433. (In Russ.)]
  13. Тюняева Н.О., Софронова Л.В. Инфекционный мононуклеоз: этиологические факторы, проблемы диагностики и лечения (научный обзор) // Вестник новых медицинских технологий. 2014. Т. 21, № 3. С. 185–190. [Tyunyaeva N.O., Sofronova L.V. Infectious mononucleosis: etiological factors, diagnosis and treatment problems. Vestnik novykh meditsinskikh tekhnologii = Herald of New Medical Technologies, 2014, vol. 21, no. 3, pp. 185–190. (In Russ.)] doi: 10.12737/5932
  14. Хохлова З.А., Попова О.А., Чуйкова К.И., Якимов В.Л., Минакова Ю.В., Петрова Е.И. Инфекционный мононуклеоз у детей: особенности течения заболевания в зависимости от видов противовирусной терапии // Журнал инфектологии. 2017. T. 9, № 3. С. 67–74. [Khokhlova Z.A., Popova O.A., Chujkova K.I., Yakimov V.L., Minakova Y.V., Petrova E.I. Infectious mononucleosis at children: features of the course of the disease depending on types of antiviral therapy. Zhurnal infektologii = Journal Infectology, 2017, vol. 9, no. 3, pp. 67–74. (In Russ.)] doi: 10.22625/2072-6732-2017-9-3-67-74
  15. Andrei G., Trompet E., Snoeck R. Novel therapeutics for Epstein–Barr virus. Molecules, 2019, vol. 24, no. 5: 997. doi: 10.3390/molecules24050997
  16. Cain D.W., Cidlowski J.A. Immune regulation by glucocorticoids. Nat. Rev. Immunol., 2017, vol. 17, pp. 233–247. doi: 10.1038/nri.2017.1
  17. Ma C., Wong C.K., Chan K.C., Lun S.W., Lee N., Wu J., Cockram C.S., Chan P.K., Tang J.W. Cytokine responses in a severe case of glandular fever treated successfully with foscarnet combined with prednisolone and intravenous immunoglobulin. J. Med. Virol., 2009, vol. 81, no. 1, pp. 99–105. doi: 10.1002/jmv.21383
  18. Odumare O.A., Hogquist K.A., Balfur H.H. Progress and problems in understanding and managing primary Epstein–Barr virus infections. Clin. Microb. Rev., 2011, vol. 24, no. 1, pp. 193–209. doi: 10.1128/CMR.00044-10
  19. Rezk E., Nofal Y.H., Hamzel A., Aboujaib M.F., Al Kheder M.A., Al Hammad M.F. Steroids for symptom control in infectious mononucleosis. Cochrane Database Syst. Rev., 2015, vol. 11: CD004402. doi: 10.1002/14651858.CD004402.pub3
  20. Xing K., Gu B., Zhang P., Wu X. Dexamethasone enhances programmed cell death 1 (PD-1) expression during T cell activation: an insight into the optimum application of glucocorticoids in anti-cancer therapy. BMC Immunol., 2015, vol. 16: 39. doi: 10.1186/s12865-015-0103-2

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Copyright (c) 2021 Fedorova I.M., Koteleva S.I., Kapustin I.V., Blyakher M.S., Tulskaya E.A., Zvereva N.N., Ilina M.A., Saifullin M.A., Samkov A.A., Vlasov E.V.

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