Research Article
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Pediatrik Şiddetli Pnömoni Vakalarında IL-21, IL-23 ve 8-hidroksi-2'-deoksiguanozin Serum Düzeyleri

Year 2023, , 463 - 469, 31.12.2023
https://doi.org/10.35440/hutfd.1285583

Abstract

Objective: Pneumonia causes the majority of acute respiratory distress syndrome (ARDS) cases. The microbes that cause pneumonia are very diverse. In addition, RNA viruses, DNA viruses, enveloped viruses, non-enveloped viruses, Gram positive and negative bacteria affect the imbalance in two types of cytokines, pro inflammatory and anti-inflammatory, and may affect the prognosis of sepsis and other infectious and inflammatory diseases. The aim of the study was to compare clinical features and cytokine levels in young patients with severe pneumonia who require investigation of IL-21, IL-23, 8-hydroxy-2′-deoxyguanosine (8-OHdG) and c-reactive protein (CRP) levels in pediatric pneumonia patients to determine whether cytokine levels are associated with outcome in pediatric cases of severe pneumonia.
Method: In this study, blood was drawn to investigate serum IL-21, IL-23, 8-OHdG and CRP levels in approximately 43 with pediatric pneumonia patients and 43 healthy controls who came to the pediatric clinic. The levels of tested Biomarkers were studied by Elisa method and CRP levels of the serum were measured using Atellica IM Analyzer.
Results: Serum IL-21, IL-23, 8-OHdG and CRP levels were significantly higher in pediatric pneumonia patients group compared to the control group. Statistically significant differences were observed between the groups.
Conclusion: Our results showing increased serum IL-21, IL-23, 8-OHdG and CRP expression in pediatric pneumonia patients concluded that it is a potential determinant, suggesting that IL-21, IL-23-related cytokines may play a role in endothelial cell activation reported in patients. Increased 8-OHdG oxidative stress is more pronounced in patients without pediatric pneumonia while pro inflammatory cytokines are higher in pediatric pneumonia patients. Further studies on the impact of these findings on comorbidities. However, their true significance may serve as a possible therapeutic target for reducing inflammation. To test these concepts, additional preclinical trials and clinical trials with larger cohort sizes will be required.

Supporting Institution

HÜBAK

Project Number

21125

References

  • 1. Henriques-Normark B, Tuomanen EI. The pneumococcus: epidemiology, microbiology, and pathogenesis. Cold Spring Harbor perspectives in medicine. Cold Spring Harb Perspect Med. 2013; 3(7):a010215. Doi: 10.1101/cshperspect.a010215
  • 2. Nair H, Simões EA, Rudan I, Gessner BD, Azziz-Baumgartner E, Zhang JSF et al. Global and region al burden of hospital ad-missions for severe acute lower respiratory infections in young children in 2010: a systematic analysis. Lancet. 2013; 381(9875): 1380–90. Doi: 10.1016/S0140-6736(12)61901-1
  • 3. Jackson S, Mathews KH, Pulanic D, Falconer R, Rudan I, Campbell H, et al. Risk factors for severe acute lower respira-tory infections in children – a systematic review and meta-analysis. Croat Med J. 2013; 54(2):110–21. Doi: 10.3325/cmj.2013.54.110.
  • 4. Neil D. Ritchie1, Ryan Ritchie1, Hannah K. Bayes1, Tim J. et al. IL-17 can be protective or deleterious in murine pneumococ-cal pneumonia. 2018; 14(5):e1007099. Doi: 10.1371/journal.ppat.1007099.
  • 5. Päiväniemi OE, Maasilta PK, Vainikka TL, Alho HS, Karhunen PJ, Salminen US. Local C-reactive protein expression in oblit-erative lesions and the bronchial wall in posttrans plant oblit-erative bronchiolitis. Mediators Inflamm. 2009; 2009:510254. Doi: 10.1155/2009/510254
  • 6. Melissa M. Higdon, Tham Le, Katherine L. O’Brien, David R. et al. Association of C-reactive protein with bacterial and respir-atory syncytial virus–associated pneumonia among children aged<5 years in the perch study. Clin Infect Dis. 2017; 64(Suppl 3): S378–S386. Doi: 10.1093/cid/cix150
  • 7. Moberg Anna B, Ravell JA, Paues J, Magnus F. C-reactive protein influences the doctor’s degree of suspicion of pneu-monia in primary care: a prospective observational study. Eur J Gen Pract. 2020; 26(1): 210–216. Doi: 10.1080/13814788.2020.1852547
  • 8. Dukhinova M, Kokinos E, Kuchur P, Komissarov A, Shtro A. Macrophage-derived cytokines in pneumonia: Linking cellular immunology and genetics. Cytokine Growth Factor Rev. 2021; 59:46–61. Doi: 10.1016/j.cytogfr.2020.11.003.
  • 9. Antalis E, Spathis A, Kottaridi C, Kossyvakis A, Pastellas K, Tsakalos K, et al. Th17 serum cytokines in relationtolaborato-ry‐confirmed respiratory viral infection: A pilot study. J Med Virol. 2019; 91(6):963–71. Doi: 10.1002/jmv.25406
  • 10. de Araujo OR, Salomão R, Karina M, Brunialti C, da Silva DCB, Senerchia AA, et al. cytokine kinetics in febrile neutropenic children: insights on the usefulness as sepsis biomarkers, in-fluence of filgrastim, and behavior of the il-23/il-17 pathway. mediators inflamm. 2017, Doi: 10.1155/2017/8291316.
  • 11. Keven M Robinson , Michelle L Manni, Partha S Biswas, John F Alcorn. Clinical consequences of targeting il-17 and th17 in au-toimmune and allergic disorders. curr allergy asthma rep. au-thor manuscript; available in PMC 2014, Curr Allergy Asthma Rep. 2013; 13(6): 587-95. Doi: 10.1007/s11882-013-0361-0
  • 12. Guo X, Cui H, Zhang H, Guan X, Zhang Z, Jia C, et al. Protective effect of folic acid on oxidative dna damage: a randomized, double-blind, and placebo controlled clinical trial. Medicine (Baltimore) 2015; 94(45):e1872. Doi: 10.1097/MD.0000000000001872.
  • 13. Xu W, Tingting Z, Xiao H. The implication of oxidative stress and ampk-nrf 2 antioxidative signaling in pneumonia patho-genesis. Front Endocrinol (Lausanne). 2020; 11: 400. Doi: 10.3389/fendo.2020.00400
  • 14. Niu B-Y, Li W-K, Li,J-S Hong Q-H, Khodahemmati S, Gao J-F,et al. Effects of DNA damage and oxidative stress in human. Bronchial Epithelial Cells Exposed to PM2.5 from Beijing, Chi-na, in Winter. Int J Environ Res Public Health. 2020; 17(13):4874. Doi: 10.3390/ijerph17134874
  • 15. Black CN, Bot M, Scheffer PG, Brenda W. Penninx JH. Socio demographic and Life style Determinants of plasma oxidative stress markers 8-ohdg and f2-isoprostanes and associations with metabolic syndrome. Oxid Med Cell Longev. 2016;2016:7530820, Doi: 10.1155/2016/7530820
  • 16. Musolino MA, Tomà P, Rose CD, Pitaro E, Boccuzzi E, De Santis R, et al. Ten years of pediatric lung ultrasound: A Narra-tive Review. Front Physiol. 2021; 12:721951. Doi: 10.3389/fphys.2021.721951
  • 17. Eshwara VK, Mukhopadhyay C, Rello J. Community-acquired bacterial pneumonia in adults: An update. Indian J Med Res. 2020; 151(4):287–302. Doi: 10.4103/ijmr.IJMR_1678_19
  • 18. Thidieu TN, Nhat AP, Craig TJ, Duong-Quy S. Clinical character-istics and cytokine changes in children with pneumonia re-quiring mechanical ventilation. J Int Med Res. 2017; 45(6):1805-17. Doi: 10.1177/0300060516672766.
  • 19. de Coelho RC, de Brito M, Lucena-Silva N, Cavalcante Torres L, Luna CF. The balance between the serum levels of IL-6 and IL-10 cytokines discriminates mild and severe acute pneumo-nia. BMC Pulm Med. 2016; 16(1):170. Doi: 10.1186/s12890-016-0324-z
  • 20. Hsu Dl, Taylor P, Fletcher D, Heeckeren RV, Eastman J, Heeckeren AV. Interleukin-17 pathophysiology and thera-peutic intervention in cystic fibrosis lung infection and in-flammation. Infect Immun. 2016; 84(9):2410-28. Doi: 10.1128/IAI.00284-16
  • 21. Fu BRT, Rong C, Liu W, Li HK. Association between serum CCL-18 and IL-23 concentrations and disease progression of chronic obstructive pulmonary disease. Sci Rep. 2020; 10(1):17756. doi: 10.1038/s41598-020-73903-6.
  • 22. Paidipally P, Tripathi D, Van A, Rad hakrishnan RK, Dhiman R, Venkatasubramanian S, et al. Interleukin-21 regulates natural killer cell responses during mycobacterium tuberculosis infec-tion. J Infect Dis. 2018; 217(8):1323–33. Doi: 10.1093/infdis/jiy034
  • 23. Rong B, Fu T, Rong C, Liu W, Li K, Liu H. Association between serum CCL-18 and IL-23 concentrations and disease progres-sion of chronic obstructive pulmonary disease. Sci Rep. 2020 10(1):17756. Doi: 10.1038/s41598-020-73903-6.
  • 24. Patricia J. Dubin, Ashley Martz, Jessica R. Eisenstatt, Michael D. Fox, Alison Logar, Jay K. Kolls. Interleukin-23-mediated in-flammation in Pseudomonas aeruginosa pulmonary infection. Infect Immun. 2012; 80(1):398–409. Doi: 10.1128/IAI.05821-11
  • 25. Olszowiec-Chlebna M, Koniarek-Maniecka A, Brzozowska A, Błauż A, Rychlik B, Stelmach I. Vitamin D inhibits pro-inflammatory cytokines in the airways of cystic fibrosis pa-tients infected by Pseudomonas aeruginosa- pilot study. Ital J Pediatr. 2019; 45(1)41. Doi: 10.1186/s13052-019-0634-x
  • 26. Podsiad A, Standiford T J, Ballinger M N, Eakin R, Park P, Kun-kel S L.Micro RNA-155 regulates host immune response to postviral bacterial pneumonia via IL-23/IL-17 pathway. Am J Physiol Lung Cell Mol Physiol. 2016; 310(5):L465–L475. Doi: 10.1152/ajplung.00224.2015
  • 27. Endeman H, Meijvis SC, Rijkers GT, vanVelzen-Blad H, van-Moorsel CH, Grutters JC,et al. Systemic cytokine response in patients with community-acquired pneumonia. Eur Respir J. 2011; 37(6):1431-8. Doi: 10.1183/09031936.00074410.
  • 28. Moberg AB., Jensen AR, Paues J, Magnus F. C-reactive pro-tein influence sthe doctor’s degree of suspicion of pneumo-nia in primary care: a prospective observational study. Eur J Gen Pract. 2020; 26(1): 210–16. Doi: 10.1080/13814788.2020.1852547
  • 29. Chen P, Huang Z, Chen L, Zhuang S, Lin H, Xie J. The relation-ships between LncRNA NNT-AS1, CRP, PCT and their interac-tions and there fractory mycoplasma pneumoniae pneumo-nia in children. Sci Rep. 2021; 11(1):2059. Doi: 10.1038/s41598-021-81853-w
  • 30. Graille M, Wild P, Sauvain J-J, Hemmendinger M, Canu IG 1, Hopf N B. Urinary 8-OHdG as a biomarker for oxidative stress: A systematic literature review and meta-analysis. Int J Mol Sci. 2020, 21, 3743; Doi:10.3390/ijms21113743
  • 31. Watanabe S, Li Y‐S, Kawasaki Y, Ootsuyama Y, Kawai K. Health examination results and work environment factors affecting urinary 8‐hydroxy‐2′‐deoxyguanosine levels. J Occup Health. 2021; 63(1): e12210. Doi: 10.1002/1348-9585.12210
  • 32. Cao O, Zhou Y, Tan A, Shi T, Zhu C, Xiao L, et al. Oxidative damage mediates the association between polycyclic aro-matic hydrocarbon exposure and lung function Environ Health. 2020; 19(1):75. Doi: 10.1186/s12940-020-00621-x.

Serum Levels of IL-21, IL-23 and 8-hydroxy-2′-deoxyguanosine in Pediatric Severe Pneumonia Cases

Year 2023, , 463 - 469, 31.12.2023
https://doi.org/10.35440/hutfd.1285583

Abstract

Background: Pneumonia causes the majority of acute respiratory distress syndrome (ARDS) cases. The microbes that cause pneumonia are very diverse. In addition to DNA, RNA viruses, Gram-negative and Gram-positive bacteria cause two types of cytokine imbalances, anti-inflammatory and pro-inflammatory. It can also influence the progno-sis of sepsis and other infectious diseases. This study aims to search for 8-hydroxy-2'-deoxyguanosine (8-OHdG), IL-21, IL-23, and c-reactive protein (CRP) and compare cytokine levels. It is also to determine if Pediatric pneumonia patients CRP and cytokine levels correlate with results.
Materials and Methods: In the study, blood was drawn from approximately 43 pediatric pneumonia patients and 43 healthy controls who came to the pediatric clinic to investigate serum IL-21, IL-23, 8-OHdG, and CRP levels. The levels of biomarkers were determined by ELISA method. Serum CRP levels were measured using the ATELLICA IM Analyzer.
Results: Serum CRP, 8-OHdG, IL-21 and IL-23 levels were significantly higher in the pediatric pneumonia patient group than in the control group.
Conclusions: Increased serum IL-21, IL-23, 8-OHdG and CRP expression in pediatric pneumonia patients is a poten-tial determinant suggesting that IL-21, IL-23-related cytokines may play a role in endothelial cell activation reported in patients. Increased 8-OHdG oxidative stress is more pronounced in patients without pediatric pneumonia while pro inflammatory cytokines are higher in pediatric pneumonia patients. However, it is used as a possible therapeu-tic target to reduce inflammation. Further study on the impact of these findings on comorbidities with larger num-ber test size is needed

Project Number

21125

References

  • 1. Henriques-Normark B, Tuomanen EI. The pneumococcus: epidemiology, microbiology, and pathogenesis. Cold Spring Harbor perspectives in medicine. Cold Spring Harb Perspect Med. 2013; 3(7):a010215. Doi: 10.1101/cshperspect.a010215
  • 2. Nair H, Simões EA, Rudan I, Gessner BD, Azziz-Baumgartner E, Zhang JSF et al. Global and region al burden of hospital ad-missions for severe acute lower respiratory infections in young children in 2010: a systematic analysis. Lancet. 2013; 381(9875): 1380–90. Doi: 10.1016/S0140-6736(12)61901-1
  • 3. Jackson S, Mathews KH, Pulanic D, Falconer R, Rudan I, Campbell H, et al. Risk factors for severe acute lower respira-tory infections in children – a systematic review and meta-analysis. Croat Med J. 2013; 54(2):110–21. Doi: 10.3325/cmj.2013.54.110.
  • 4. Neil D. Ritchie1, Ryan Ritchie1, Hannah K. Bayes1, Tim J. et al. IL-17 can be protective or deleterious in murine pneumococ-cal pneumonia. 2018; 14(5):e1007099. Doi: 10.1371/journal.ppat.1007099.
  • 5. Päiväniemi OE, Maasilta PK, Vainikka TL, Alho HS, Karhunen PJ, Salminen US. Local C-reactive protein expression in oblit-erative lesions and the bronchial wall in posttrans plant oblit-erative bronchiolitis. Mediators Inflamm. 2009; 2009:510254. Doi: 10.1155/2009/510254
  • 6. Melissa M. Higdon, Tham Le, Katherine L. O’Brien, David R. et al. Association of C-reactive protein with bacterial and respir-atory syncytial virus–associated pneumonia among children aged<5 years in the perch study. Clin Infect Dis. 2017; 64(Suppl 3): S378–S386. Doi: 10.1093/cid/cix150
  • 7. Moberg Anna B, Ravell JA, Paues J, Magnus F. C-reactive protein influences the doctor’s degree of suspicion of pneu-monia in primary care: a prospective observational study. Eur J Gen Pract. 2020; 26(1): 210–216. Doi: 10.1080/13814788.2020.1852547
  • 8. Dukhinova M, Kokinos E, Kuchur P, Komissarov A, Shtro A. Macrophage-derived cytokines in pneumonia: Linking cellular immunology and genetics. Cytokine Growth Factor Rev. 2021; 59:46–61. Doi: 10.1016/j.cytogfr.2020.11.003.
  • 9. Antalis E, Spathis A, Kottaridi C, Kossyvakis A, Pastellas K, Tsakalos K, et al. Th17 serum cytokines in relationtolaborato-ry‐confirmed respiratory viral infection: A pilot study. J Med Virol. 2019; 91(6):963–71. Doi: 10.1002/jmv.25406
  • 10. de Araujo OR, Salomão R, Karina M, Brunialti C, da Silva DCB, Senerchia AA, et al. cytokine kinetics in febrile neutropenic children: insights on the usefulness as sepsis biomarkers, in-fluence of filgrastim, and behavior of the il-23/il-17 pathway. mediators inflamm. 2017, Doi: 10.1155/2017/8291316.
  • 11. Keven M Robinson , Michelle L Manni, Partha S Biswas, John F Alcorn. Clinical consequences of targeting il-17 and th17 in au-toimmune and allergic disorders. curr allergy asthma rep. au-thor manuscript; available in PMC 2014, Curr Allergy Asthma Rep. 2013; 13(6): 587-95. Doi: 10.1007/s11882-013-0361-0
  • 12. Guo X, Cui H, Zhang H, Guan X, Zhang Z, Jia C, et al. Protective effect of folic acid on oxidative dna damage: a randomized, double-blind, and placebo controlled clinical trial. Medicine (Baltimore) 2015; 94(45):e1872. Doi: 10.1097/MD.0000000000001872.
  • 13. Xu W, Tingting Z, Xiao H. The implication of oxidative stress and ampk-nrf 2 antioxidative signaling in pneumonia patho-genesis. Front Endocrinol (Lausanne). 2020; 11: 400. Doi: 10.3389/fendo.2020.00400
  • 14. Niu B-Y, Li W-K, Li,J-S Hong Q-H, Khodahemmati S, Gao J-F,et al. Effects of DNA damage and oxidative stress in human. Bronchial Epithelial Cells Exposed to PM2.5 from Beijing, Chi-na, in Winter. Int J Environ Res Public Health. 2020; 17(13):4874. Doi: 10.3390/ijerph17134874
  • 15. Black CN, Bot M, Scheffer PG, Brenda W. Penninx JH. Socio demographic and Life style Determinants of plasma oxidative stress markers 8-ohdg and f2-isoprostanes and associations with metabolic syndrome. Oxid Med Cell Longev. 2016;2016:7530820, Doi: 10.1155/2016/7530820
  • 16. Musolino MA, Tomà P, Rose CD, Pitaro E, Boccuzzi E, De Santis R, et al. Ten years of pediatric lung ultrasound: A Narra-tive Review. Front Physiol. 2021; 12:721951. Doi: 10.3389/fphys.2021.721951
  • 17. Eshwara VK, Mukhopadhyay C, Rello J. Community-acquired bacterial pneumonia in adults: An update. Indian J Med Res. 2020; 151(4):287–302. Doi: 10.4103/ijmr.IJMR_1678_19
  • 18. Thidieu TN, Nhat AP, Craig TJ, Duong-Quy S. Clinical character-istics and cytokine changes in children with pneumonia re-quiring mechanical ventilation. J Int Med Res. 2017; 45(6):1805-17. Doi: 10.1177/0300060516672766.
  • 19. de Coelho RC, de Brito M, Lucena-Silva N, Cavalcante Torres L, Luna CF. The balance between the serum levels of IL-6 and IL-10 cytokines discriminates mild and severe acute pneumo-nia. BMC Pulm Med. 2016; 16(1):170. Doi: 10.1186/s12890-016-0324-z
  • 20. Hsu Dl, Taylor P, Fletcher D, Heeckeren RV, Eastman J, Heeckeren AV. Interleukin-17 pathophysiology and thera-peutic intervention in cystic fibrosis lung infection and in-flammation. Infect Immun. 2016; 84(9):2410-28. Doi: 10.1128/IAI.00284-16
  • 21. Fu BRT, Rong C, Liu W, Li HK. Association between serum CCL-18 and IL-23 concentrations and disease progression of chronic obstructive pulmonary disease. Sci Rep. 2020; 10(1):17756. doi: 10.1038/s41598-020-73903-6.
  • 22. Paidipally P, Tripathi D, Van A, Rad hakrishnan RK, Dhiman R, Venkatasubramanian S, et al. Interleukin-21 regulates natural killer cell responses during mycobacterium tuberculosis infec-tion. J Infect Dis. 2018; 217(8):1323–33. Doi: 10.1093/infdis/jiy034
  • 23. Rong B, Fu T, Rong C, Liu W, Li K, Liu H. Association between serum CCL-18 and IL-23 concentrations and disease progres-sion of chronic obstructive pulmonary disease. Sci Rep. 2020 10(1):17756. Doi: 10.1038/s41598-020-73903-6.
  • 24. Patricia J. Dubin, Ashley Martz, Jessica R. Eisenstatt, Michael D. Fox, Alison Logar, Jay K. Kolls. Interleukin-23-mediated in-flammation in Pseudomonas aeruginosa pulmonary infection. Infect Immun. 2012; 80(1):398–409. Doi: 10.1128/IAI.05821-11
  • 25. Olszowiec-Chlebna M, Koniarek-Maniecka A, Brzozowska A, Błauż A, Rychlik B, Stelmach I. Vitamin D inhibits pro-inflammatory cytokines in the airways of cystic fibrosis pa-tients infected by Pseudomonas aeruginosa- pilot study. Ital J Pediatr. 2019; 45(1)41. Doi: 10.1186/s13052-019-0634-x
  • 26. Podsiad A, Standiford T J, Ballinger M N, Eakin R, Park P, Kun-kel S L.Micro RNA-155 regulates host immune response to postviral bacterial pneumonia via IL-23/IL-17 pathway. Am J Physiol Lung Cell Mol Physiol. 2016; 310(5):L465–L475. Doi: 10.1152/ajplung.00224.2015
  • 27. Endeman H, Meijvis SC, Rijkers GT, vanVelzen-Blad H, van-Moorsel CH, Grutters JC,et al. Systemic cytokine response in patients with community-acquired pneumonia. Eur Respir J. 2011; 37(6):1431-8. Doi: 10.1183/09031936.00074410.
  • 28. Moberg AB., Jensen AR, Paues J, Magnus F. C-reactive pro-tein influence sthe doctor’s degree of suspicion of pneumo-nia in primary care: a prospective observational study. Eur J Gen Pract. 2020; 26(1): 210–16. Doi: 10.1080/13814788.2020.1852547
  • 29. Chen P, Huang Z, Chen L, Zhuang S, Lin H, Xie J. The relation-ships between LncRNA NNT-AS1, CRP, PCT and their interac-tions and there fractory mycoplasma pneumoniae pneumo-nia in children. Sci Rep. 2021; 11(1):2059. Doi: 10.1038/s41598-021-81853-w
  • 30. Graille M, Wild P, Sauvain J-J, Hemmendinger M, Canu IG 1, Hopf N B. Urinary 8-OHdG as a biomarker for oxidative stress: A systematic literature review and meta-analysis. Int J Mol Sci. 2020, 21, 3743; Doi:10.3390/ijms21113743
  • 31. Watanabe S, Li Y‐S, Kawasaki Y, Ootsuyama Y, Kawai K. Health examination results and work environment factors affecting urinary 8‐hydroxy‐2′‐deoxyguanosine levels. J Occup Health. 2021; 63(1): e12210. Doi: 10.1002/1348-9585.12210
  • 32. Cao O, Zhou Y, Tan A, Shi T, Zhu C, Xiao L, et al. Oxidative damage mediates the association between polycyclic aro-matic hydrocarbon exposure and lung function Environ Health. 2020; 19(1):75. Doi: 10.1186/s12940-020-00621-x.
There are 32 citations in total.

Details

Primary Language English
Subjects Clinical Sciences
Journal Section Research Article
Authors

Nihayet Bayraktar 0000-0002-5745-9678

Ahmet Güzelçiçek 0000-0002-9733-3957

Ali Öztürk 0000-0003-2428-1831

Mehmet Bayraktar 0000-0003-2306-6531

Hamza Erdoğdu 0000-0002-5025-2367

Project Number 21125
Early Pub Date October 6, 2023
Publication Date December 31, 2023
Submission Date April 19, 2023
Acceptance Date July 20, 2023
Published in Issue Year 2023

Cite

Vancouver Bayraktar N, Güzelçiçek A, Öztürk A, Bayraktar M, Erdoğdu H. Serum Levels of IL-21, IL-23 and 8-hydroxy-2′-deoxyguanosine in Pediatric Severe Pneumonia Cases. Harran Üniversitesi Tıp Fakültesi Dergisi. 2023;20(3):463-9.

Harran Üniversitesi Tıp Fakültesi Dergisi  / Journal of Harran University Medical Faculty