Preview

Medical Immunology (Russia)

Advanced search

Cytokine profile in community-acquired pneumonia in children

https://doi.org/10.15789/1563-0625-CPI-2538

Abstract

Community-acquired pneumonia (CAP) is one of the most common acute infectious diseases. To date, the incidence of CAP among children was decreased significantly worldwide, mainly due to increasing use of effective preventive measures. Nevertheless, CAP remains a common cause of childhood morbidity and mortality. Pneumonia may develop at any age, but most often it occurs in young children, who are more likely to have a more severe course of pneumonia. Currently, early diagnosis and prognosis of the disease severity in children is an urgent issue. It was found that, in most cases, a panel of conventional biomarkers, including the number of leukocytes, procalcitonin, CRP is not sufficient for the diagnosis of pediatric CAP. There is a demand for new biological markers which, along with clinical evaluation, may significantly improve diagnostics and management of CAP in children, thus reducing the risk of adverse outcomes associated with this disease. Such markers could be found among the cytokines, which are active participants in the CAP pathogenesis. The aim of this study was to determine the level of several cytokines in blood serum of children with CAP and to assess changes in the cytokine profile depending on the patient’s age and severity of the disease. The study included 117 children aged 1 to 18 years with a diagnosis of CAP confirmed by X-ray examination. The comparison group included 28 healthy children who did not have CAP or other signs of acute respiratory viral infection at the time of examination, being free of any chronic pathology requiring outpatient observation. A number of cytokines were determined quantitatively in blood serum, i.e., IL-1β, IFNγ, IL-2, IL-4, IL-6, IL-10, TNFα, IFNλ2 (IL-28A), IFNλ3 (IL-28B), IL-8, MCP-1, IL-17AF, GM-CSF using test systems based on the “sandwich” method of solid-phase ELISA using peroxidase labeling. As a result, it was found that the content of IL-6, IL-17AF, IL-1β, IFNγ, MCP-1, IFNλ2 (IL-28A), IFNλ3 (IL-28B), GM-CSF was significantly higher in the group of children with severe community-acquired pneumonia. The levels of certain cytokines, e.g., IL-6, IFNλ2 (IL-28A), IFNλ3 (IL-28B), GM-CSF varied depending on the age of patients, thus, probably, reflecting the degree of immune system activation in the children of different age groups.

About the Authors

N. V. Iziurova
South Ural Medical State University
Russian Federation

Iziurova Natalia V. Assistant Professor, Department of Propaedeutics of Children’s Diseases and Pediatrics

454092, Chelyabinsk, Vorovsky str., 64
Phone: 7 (963) 081-46-78



A. Yu. Savochkina
South Ural Medical State University
Russian Federation

PhD, MD (Medicine), Professor, Department of Clinical Laboratory Diagnostics

Chelyabinsk



A. N. Uzunova
South Ural Medical State University
Russian Federation

PhD, MD (Medicine), Professor, Head, Department of Propaedeutics of Children’s Diseases and Pediatrics

Chelyabinsk



D. Yu. Nokhrin
Chelyabinsk State University
Russian Federation

PhD (Biology), Associate Professor, Department of Microbiology, Immunology and General Biology, Faculty of Biology

Chelyabinsk



References

1. Geppe N.A., Malakhov A.B., Dronov I.A., Khabibullina E.A. Community-acquired pneumonia in children: problems of diagnosis, treatment and prevention. Doktor.Ru = Doktor.Ru, 2015, no. 13 (114), pp. 20-27. (In Russ.)

2. Zaitseva O.V. Formation of immunity: topical issues of pediatrics. Allergologiya i immunologiya v pediatrii = Allergology and Immunology in Pediatrics, 2014, no. 2 (37), pp. 12-22. (In Russ.)

3. Pikuza O.I., Samorodnova E.A. Modern features of community-acquired pneumonia in young children. Prakticheskaya meditsina = Practical Medicine, 2013, no. 6 (75), pp. 35-41. (In Russ.)

4. Pneumonia (community-acquired). Original layout, 2022. 82 p. [Electronic resource]. Access mode: https://cr.minzdrav.gov.ru/schema/714_1.

5. Uzunova A.N. Pneumonia in childhood. Chelyabinsk: Chelyabinsk State Medical Academy, 2002. 215 p.

6. Bacci M.R., Leme R.C., Zing N.P., Murad N., Adami F., Hinnig P.F., Feder D., Chagas A.C., Fonseca F.L. IL-6 and TNF-α serum levels are associated with early death in community-acquired pneumonia patients. Braz. J. Med. Biol. Res., 2015, Vol. 48, no. 5, pp. 427-432.

7. Banerjee R. CON: Procalcitonin does not have clinical utility in children with community-acquired pneumonia. JAC Antimicrob. Resist., 2021, Vol. 3, no. 4, dlab152. doi: 10.1093/jacamr/dlab152.

8. Bonaventura A., Vecchié A., Wang T.S., Lee E., Cremer P.C., Carey B., Rajendram P., Hudock K.M., Korbee L., van Tassell B.W., Dagna L., Abbate A. Targeting GM-CSF in COVID-19 Pneumonia: Rationale and Strategies. Front. Immunol., 2020, Vol. 11, 1625. doi: 10.3389/fimmu.2020.01625.

9. de Brito R.C., Lucena-Silva N., Torres L.C., Luna C.F., Correia J.B., da Silva G.A. The balance between the serum levels of IL-6 and IL-10 cytokines discriminates mild and severe acute pneumonia. BMC Pulm. Med., 2016, Vol. 16, no. 1, 170. doi: 10.1186/s12890-016-0324-z.

10. Fernandes C.D., Arriaga M.B., Costa M.C.M., Costa M.C.M., Costa M.H.M., Vinhaes C.L., SilveiraMattos P.S., Fukutani K.F., Andrade B.B. Host inflammatory biomarkers of disease severity in pediatric community-acquired pneumonia: a systematic review and meta-analysis. Open Forum Infect. Dis., 2019, Vol. 6, no. 12, ofz520. doi: 10.1093/ofid/ofz520.

11. Fukuda Y., Homma T., Inoue H., Onitsuka C., Ikeda H., Goto Y., Sato Y., Kimura T., Hirai K., Ohta S., Yamamoto M., Kusumoto S., Suzuki S., Tanaka A., Sagara H. Downregulation of type III interferons in patients with severe COVID-19. J. Med. Virol., 2021, Vol. 93, no. 7, pp. 4559-4563.

12. Galani I.E., Rovina N., Lampropoulou V., Triantafyllia V., Manioudaki M., Pavlos E., Koukaki E., Fragkou P.C., Panou V., Rapti V., Koltsida O., Mentis A., Koulouris N., Tsiodras S., Koutsoukou A., Andreakos E. Untuned antiviral immunity in COVID-19 revealed by temporal type I/III interferon patterns and flu comparison. Nat. Immunol., 2021, Vol. 22, no. 1, pp. 32-40.

13. Hammer O., Harper D.A.T., Ryan P.D. PAST: Paleontological Statistics Software Package for Education and Data Analysis. Palaeontologia Electronica, 2001, Vol. 4, iss. 1, 9 p. Available at: https://palaeo-electronica.org/2001_1/past/issue1_01.htm.

14. Haugen J., Chandyo R.K., Brokstad K.A., Mathisen M., Ulak M., Basnet S., Valentiner-Branth P., Strand T.A. Cytokine concentrations in plasma from children with severe and non-severe community acquired pneumonia. PLoS One, 2015, Vol. 10, no. 9, e0138978. doi: 10.1371/journal.pone.0138978.

15. Jin H.L., Zhan L., Mei S.F., Shao Z.Y. Serum cytokines and FeNO in school-aged children with mycoplasma pneumoniae pneumonia. Med. Sci. Monit., 2020, Vol. 26, e923449. doi: 10.12659/MSM.923449.

16. Khaedir Y., Kartika R. Perspectives on Targeting IL-6 as a Potential Therapeutic Strategy for COVID-19. J. Interferon Cytokine Res., 2021, Vol. 41, no. 2, pp. 37-43.

17. Kleiner G., Marcuzzi A., Zanin V., Monasta L., Zauli G. Cytokine levels in the serum of healthy subjects. Mediators Inflamm., 2013, Vol. 2013, 434010. doi: 10.1155/2013/434010.

18. le Roux D.M., Zar H.J. Community-acquired pneumonia in children – a changing spectrum of disease. Pediatr. Radiol., 2017, Vol. 47, no. 11, pp. 1392-1398.

19. Lee J.E., Kim J.W., Han B.G., Shin S.Y. Impact of whole-blood processing conditions on plasma and serum concentrations of cytokines. Biopreserv. Biobank., 2016, Vol. 14, no. 1, pp. 51-55.

20. Liu C., Chu D., Kalantar-Zadeh K., George J., Young H.A., Liu G. Cytokines: from clinical significance to quantification. Adv. Sci. (Weinh), 2021, Vol. 8, no. 15, e2004433. doi: 10.1002/advs.202004433.

21. Liu M., Lu B., Fan H., Guo X., Du S., Yang D., Xu Y., Li Y., Che D., Liu Y., Gu X., Ding T., Wang P., Luo H.B., Lu G. Heightened local Th17 cell inflammation is associated with severe community-acquired pneumonia in children under the age of 1 year. Mediators Inflamm. , 2021, Vol. 2021, 9955168. doi: 10.1155/2021/9955168.

22. Potere N., Batticciotto A., Vecchié A., Porreca E., Cappelli A., Abbate A., Dentali F., Bonaventura A. The role of IL-6 and IL-6 blockade in COVID-19. Expert Rev. Clin. Immunol., 2021, Vol. 17, no. 6, pp. 601-618.

23. Principi N., Esposito S. Biomarkers in pediatric community-acquired pneumonia. Int. J. Mol. Sci., 2017, Vol. 18, no. 2, 447. doi: 10.3390/ijms18020447.

24. Ritchie N.D., Ritchie R., Bayes H.K., Mitchell T.J., Evans T.J. IL-17 can be protective or deleterious in murine pneumococcal pneumonia. PLoS Pathog., 2018, Vol. 14, no. 5, e1007099. doi: 10.1371/journal.ppat.1007099.

25. Rose-John S. Interleukin-6 family cytokines. Cold Spring Harb. Perspect. Biol., 2018, Vol. 10, no. 2, a028415. doi: 10.1101/cshperspect.a028415.

26. Saghafian-Hedengren S., Mathew J.L., Hagel E., Singhi S., Ray P., Ygberg S., Nilsson A. Assessment of cytokine and chemokine signatures as potential biomarkers of childhood community-acquired pneumonia severity: a nested cohort study in india. Pediatr. Infect. Dis. J., 2017, Vol. 36, no. 1, pp. 102-108.

27. Sokal R.R., Rohlf F.J. Biometry, the principles and practice of statistics in biological research, 3 rd ed.; W.H. Freeman and Co.: New York, NY, USA, 1997.

28. Stanifer M.L., Guo C., Doldan P., Boulant S. Importance of Type I and III interferons at respiratory and intestinal barrier surfaces. Front. Immunol., 2020, Vol. 11, 608645. doi: 10.3389/fimmu.2020.608645.

29. Wilson R., Cohen J.M., Jose R.J., de Vogel C., Baxendale H., Brown J.S. Protection against Streptococcus pneumoniae lung infection after nasopharyngeal colonization requires both humoral and cellular immune responses. Mucosal Immunol., 2015, Vol. 8, no. 3, pp. 627-639.

30. World Health Organization. Revised WHO Classification and Treatment of Childhood Pneumonia at Health Facilities: Evidence Summaries. Geneva: World Health Organization; 2014. Available at: https://www.ncbi.nlm.nih.gov/books/NBK264162/.

31. Ye L., Schnepf D., Staeheli P. Interferon-λ orchestrates innate and adaptive mucosal immune responses. Nat. Rev. Immunol., 2019, Vol. 19, no. 10, pp. 614-625.

32. Yong K.K., Chang J.H., Chien M.H., Tsao S.M., Yu M.C., Bai K.J., Tsao T.C., Yang S.F. Plasma Monocyte chemoattractant protein-1 level as a predictor of the severity of community-Acquired Pneumonia. Int. J. Mol. Sci., 2016, Vol. 17, no. 2, 179. doi: 10.3390/ijms17020179.

33. Yoshioka K. KyPlot – A User-oriented Tool for Statistical Data Analysis and Visualization. CompStat, 2002, Vol. 17, iss. 3, 425-437.


Supplementary files

Review

For citations:


Iziurova N.V., Savochkina A.Yu., Uzunova A.N., Nokhrin D.Yu. Cytokine profile in community-acquired pneumonia in children. Medical Immunology (Russia). 2022;24(5):943-954. (In Russ.) https://doi.org/10.15789/1563-0625-CPI-2538

Views: 557


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1563-0625 (Print)
ISSN 2313-741X (Online)