Cytokine status indicators in children with acute respiratory viral infections after treatment with intranasal interferon-based medicine

Objective: to study the dynamics of local and systemic cytokine production in children with different clinical forms of acute respiratory viral infections (ARVI), including COVID-19, and to assess the effectiveness of local interferon-based therapy.

Patients and methods: The study included 180 patients aged from 1 month to 17 years with сonfirmed acute respiratory viral infections (ARVI), including COVID-19. Patients were divided into 2 groups (main and control) of 90 people each. In the main group patients received the intranasal interferon-based medicine Grippferon^® in addition to the basic therapy, the control group patients received only basic therapy. The cytokine status was assessed by the content of IFN-α and -γ, IL-1β, IL-8, IL-4, IL-10, IL-17 in blood serum and in nasopharyngeal secretions by enzyme immunoassay kits ("Cytokine", St. Petersburg).

Results: Statistically significant differences were revealed in the systemic and local content of individual cytokines in ARVI of different etiologies, depending on the level of damage to the respiratory tract. The use of the interferon-based medicine Grippferon^® for intranasal use in children in the early stages of ARVI, including COVID-19, helps to decrease the high content of cytokines IL-1β and IL-8 in the nasopharynx by reducing the viral load. As a result, the duration of catarrhal disease symptoms and intoxication was also significantly reduced as well as the pathogen elimination time.

1. Simbirtsev A.S. Cytokines: classification and biological functions. Cytokines and Inflammation. 2004; 3(2):16—21. (In Russ)

2. Onishi R.M., Gaffen S.L. Interleukin-17 and its target genes: mechanisms of interleukin-17 function in disease. Immunology, 2010; 129(3):311—321.

3. Henry T., Kirimanjeswara G.S., Ruby T., Jones J.W., Peng K., Perret M., Ho L., Sauer J.D., Iwakura Y., Metzger D.W., Monack D.M. Type I IFN signaling constrains IL-17A/F secretion by gammadelta T cells during bacterial infections. J Immunol, 2010; 184(7): 3755-3767.

4. Harrington L.E., Hatton R.D., Mangan P.R., Turner H., Murphy T.L., Murphy K.M., Weaver C.T. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol, 2005; 6(11):1123—1132.

5. Berezhnaya N.M., Sepiashvili R.I. Interleukin 17 family. Allergology and Immunology. 2015; 16(1):154—164. (In Russ)

6. Major J. Type I and III interferons disrupt lung epithelial repair during recovery from viral infection. J. Major. Stefania Crotta,1 Miriam Llorian2, Teresa M. McCabe1, Hans Henrik Gad3 еt аl Science 07 Aug 2020:Vol. 369, Issue 6504, pp. 712—717 DOI: 10.1126/science.abc2061

7. Patent No. 2424768 — A method for predicting the course of the disease in children with acute respiratory viral infections from 06/ 19/2009 Afanasyeva O.I., Golovacheva E.G., Kalinina N.M., Obraztsova E.V., Osidak L.V. (In Russ)

8. Golovacheva E.G., Afanasyeva V.S., Osidak L.V., Afanasieva O.I., Obraztsova E.V., Koroleva E.G., Timchenko V.N. The dynamics of the immune response to influenza in children treated with interferon. Detskie Infektsii=Children's Infections. 2017;16(1):7—12. (In Russ.) https://doi.org/10.22627/2072-8107-2017-16-1-7-12

9. Hadjadj J., Nader Yatim, Laura Barnabei, Aurélien Corneau, Jeremy Boussier et al. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science 07 Aug 2020; 369(6504):718—724 DOI: 0.1126/science.abc6027

10. Zhongji Meng, Tongyu Wang, Chen Li, Xinhe Chen, Longti Li, Xueqin Qin, Hai Li, Jie Luo. An experimental trial of recombinant human interferon alpha nasal drops to prevent coronavirus disease 2019 in medical staff in an epidemic area. https://doi.org/10.1101/2020.04.11.20061473

11. García-Sastre A. Induction and evasion of type I interferon responses by influenza viruses. Virus Res. 2011; 162(1):12—8. Doi: 10.1016/j.virusres.2011.10.01711

12. Wadman M. Can interferons stop COVID-19 before it takes hold? Science, 10 Jul 2020; 369(6500):125—126. DOI: 1126/science.369.6500.12512

13. Feldblium I.V., Devyatkov M.Yu., Gendler A.A., Maltseva S.M., Repin T.M., Nikolenko V.N. The efficacy of intranasal recombinant interferon alpha-2b for emergency prevention of covid-19 in health-care workers. Infectious Diseases. 2021; 19(1):26—32. (In Russ)

14. Khlynina Yu.O., Sharova A.A., Nevinsky A.B. The use of interferon alpha-2b for prevention of novel coronavirus infection in healthcare workers. Infectious Diseases. 2021; 19(2):65—69 (In Russ)

15. Belousov D.Yu., Cheberda A.E. Pharmacoepidemiological research: methodology and regulation. Qualitative clinical practice=Kachestvennaya klinicheskaya praktika. 2017; 1:34—41. (In Russ)

16. Gaponyuk P.Ya., Doroshenko E.M. The role of the Russian medicine Grippferon in the treatment and prevention of influenza and other acute respiratory viral infections. Poliklinika. 2008; 5:22—26. (In Russ)

17. Krasnov V.V. The effectiveness of recombinant interferon-alpha in the treatment and prevention of acute respiratory viral infections. Questions of Рractical Рediatrics. 2016; 11(4):44—52. (In Russ)

18. Osidak L. V., Afanasyeva O. I., Golovacheva E. G., et al. Recombinant interferon α-2b in the treatment and prevention of acute respiratory viral infections. Pharmateca. 2020; 27(1): 80—9. (In Russ) https://dx.doi.org/10.18565/pharmateca.2020.1.80-9

19. Collection of methodological recommendations on the isolation of viruses, IF and PCR diagnostics of influenza, the introduction of signaling surveillance data in the system. St. Petersburg: Medical News Agency, 2011:68. (In Russ)

20. Rebrova O.Yu. Statistical analysis of medical data. Application of STATISTICA package. M.: MediaSphere, 2002:312. (In Russ)

21. Voloshchuk L. V., Golovacheva E. G., Mushkatina A. L., Osidak L. V., Zarishnyuk P. V., Go A. A. Cytokine-containing drugs in the complex therapy of influenza and flu-like diseases in adults. Journal of Infectology. 2012; 4(4):52—58. (In Russ)

22. Hizawa N., Kawaguchi M., Huang S.K., Nishimura M. Role of interleukin-17F in chronic inflammatory and allergic lung disease. Clin Exp Allergy, 2006; 36(9):1109—1114.