Correlation Between I/T Ratio, S100B, Interleukin-10 Serum, and NEWS2 Score in Sepsis
-
Novianti Anggie Lestari
,
Lisyani Budipradigda Suromo
,
Meita Hendrianingtyas
,
Ariosta Setyadi
,
Dwi Retnoningrum
Abstract
Immature/total neutrophils (I/T) ratio is a simple and inexpensive method used as an early sign of bacterial infection. Meanwhile, the S100B protein is found in glial cells and functions as a neuroprotection. Then, the interleukin-10 cytokine acts as an anti-inflammatory cytokine during infection. In addition, the NEWS2 score is used to see the early and fast changes in patients with sepsis. The purpose of the study was to prove the correlation between the I/T ratio, S100B, IL-10, and NEWS2 score in patients with sepsis. A cross-sectional study was conducted on 34 patients with sepsis from September 2020 to February 2021. I/T ratio was calculated in 100 leukocytes from microscopic blood smear preparation. Levels of S100B and IL-10 serum were measured using the ELISA method. Pearson correlation test was used for normally distributed data, and the Spearman correlation test was utilized for abnormally distributed data. Correlation test between I/T ratio, S100B, and IL-10 with NEWS2 score respectively showed values of r=0.58; P=0.01, r=0.36; P=0.03, and r=0.39; P=0.02, in which P<0.05. There was a moderate positive correlation between I/T ratio and NEWS2 score, a weak positive correlation between S100B and NEWS2 score, and a weak positive correlation between IL-10 and NEWS2 score.
1. Mayr FB, Yende S, Angus DC. Epidemiology of Severe Sepsis. Virulence. 2014; 5(1):4–11.
2. Fleischmann C, Scherag A, Adhikari NKJ, Hartog CS, Tsaganos T, Schlattmann P, et al. Assessment of Global Incidence and Mortality of Hospital-treated Sepsis, Current Estimates and Limitations. Am J Resp Crit Care Med. 2016; 193(3):259–72.
3. Álvaro-Meca A, Jiménez-Sousa MA, Micheloud D, Sánchez-Lopez A, Heredia-Rodríguez M, Tamayo E, et al. Epidemiological Trends of Sepsis In The Twenty-First Century (2000-2013): An Analysis of Incidence, Mortality, and Associated Costs in Spain. Pop Health Metr. 2018;16(4):1–11.
4. Thompson K, Venkatesh B, Finfer S. Sepsis and Septic Shock: Current Approaches to Management. Intern Med J. 2019;49(2):160–70.
5. Phua J, Koh Y, Du B, Tang YQ, Divatia J V, Tan CC, et al. Management of Severe Sepsis in Patients Admitted to Asian Intensive Care Units: Prospective Cohort Study. BMJ. 2011;1-11: 452-7.
6. Tambajong RN, Lalenoh DC, Kumaat L. Profil Penderita Sepsis di ICU RSUP Prof. Dr. R. D. Kandou Manado Periode Desember 2014 – November 2015. Jurnal e-Clinic. 2016;4(1).
7. Lee YS, Choi JW, Park YH, Chung C, Park D Il, Lee JE, et al. Evaluation of the efficacy of the National Early Warning Score in predicting in-hospital mortality via the risk stratification. J Crit Care. 2018;47:222–6.
8. Mellhammar L, Linder A, Tverring J, Christensson B, Boyd JH, et al. NEWS2 Is Superior to qSOFA in Detecting Sepsis with Organ Dysfunction in the Emergency Department. J of Clin Med. 2019; 8(1128): 1–13.
9. Churpek MM, Snyder A, Han X, Sokol S, Pettit N, Howell MD, et al. Quick sepsis-related organ failure assessment, systemic inflammatory response syndrome, and early warning scores for detecting clinical deterioration in infected patients outside the intensive care unit. Am J Resp Crit Care Med. 2010;195(7):906–11.
10. Bastiana, Aryati, Iriani Y. Immature to Total Neutrophil (I/T) Ratio Sebagai Penunjang Diagnosis Sepsis Neonatorum. Indonesian Journal of Clinical Pathology and Medical Laboratory, Majalah Patologi Klinik Indonesia dan Laboratorium Medik. 2010; 16(2):73-7.
11. Henriquez-Camacho C, Losa J. Biomarkers for sepsis. Bio Research Intern. 2014; 1-6.
12. Mahalini DS. Ensefalopati pada anak dengan sepsis. SINAS Sepsis Pada Anak dan Neonatus. Fakultas Kedokteran, Universitas Udayana/RSUP Sanglah. 2011.
13. Yardan T, Erenler AK, Baydin A, Aydin K, Cokluk C. Usefulness of S100B Protein in Neurological Disorders. J Pak Med Assoc. 2011; 61(3):276-81.
14. Sun B, Liu H, Nie S. S100B Protein in Serum is Elevated After Global Cerebral Ischemic Injury. World J Emerg Med. 2013; 4(3):165–8.
15. Donato R, Sorci G, Riuzzi F, Arcuri C, Bianchi R, Brozzi F, et al. S100B’s Double Life : Intracellular Regulator and Extracellular Signal. Biochimica et Biophysica Acta. 2009;1793(6):1008–22.
16. Lobo-silva D, Carriche GM, Castro AG, Roque S, Saraiva M. Balancing the Immune Response in the Brain : IL-10 and its regulation. J of Neuroinflammation. 2016;13:297:1–10.
17. Peñaloza HF, Schultz BM, Nieto PA, Salazar GA, Suazo I, Gonzalez PA, et al. Opposing Roles of IL-10 in Acute Bacterial Infection. Cytokine & Growth Factor Reviews. 2016; 951:1-14.
18. Kotfis K, Wittebole X, Jaschinski U, Violan JS, Kashyap R, Leone M, et al. A Worldwide Perspective of Sepsis Epidemiology and Survival According to Age: Observational Data the ICON Audit. Journal of Critical Care. 2019;51:122-32.
19. Zhou J, Qian C, Zhao M, Yu X, Kang Y, Ma X, et al. Epidemiology and Outcome of Severe Sepsis and Septic Shock in Intensive Care Units in Mainland China. PLOS ONE. 2014;9(9):1-8.
20. Martin S, Perez A, Aldecoa C. Sepsis and Immunosenescence in the Elderly Patient: A Review. Frontiers in Medicine. 2017;4(20):1-10.
21. Solana R, Tarazona R, Gayoso I, Lesur O, Dupuis G, Fulop T. Innate Immunosenescence: Effect of Aging on Cells and Receptors of The Innate Immune System in Humans. Seminars In Immunology. 2012;24:331-341.
22. Agarwal S, Busse PJ. Innate and Adaptive Immunosenescence. Ann Allergy Asthma Immunol. 2010;104:183-190.
23. Chen YJ, Chen FL, Chen JH, Wu MT, Pharmd, Chen YL, et al. Epidemiology of Sepsis in Taiwan. Medicine. 2019;98(20)1-6.
24. Sakr Y, Elia C, Mascia L, Barberis B, Cardelino S, Livigni S, et al. The Influence of Gender on The Epidemiology of and Outcome from Severe Sepsis. Crit Care. 2013;17(R50):1-9.
25. Novita C, Hernaningsih Y, Wardhani P, Veterini A. The Correlation between Leucocyte CD64, Immature Granulocyte and Presepsin with Procalcitonin in Bacterial Sepsis Patient. Bali Med J. 2019;8(2):327-32.
26. Purwanto D,Astrawinata D. Mekanisme Kompleks Sepsis dan Syok Septik. Journal Biomedik. 2018;10(3):143-151.
27. Nierhaus A, Klatte S, Linssen J, Eismann N, Wichmann D, Hedke J, et al. Revisiting the White Blood Cell Count: Immature Granulocytes Count as a Diagnostic Marker to Discriminate Between SIRS and Sepsis-a Prospective, Observational Study. BMC Immunology. 2013;14(8):1-8.
28. Liu VX, Lu Y, Carey K, Gilbert E, Afshar M, Akel M, et al. Comparison of Early Warning Scoring Systems for Hospitalized Patients with and without Infection at Risk for In-Hospital Mortality and Transfer to the Intensive Care Unit. JAMA Network Open. 2020;3(5):1-12.
29. Mc Quillan S, Gordon C, Jones L, Young D. Management and Recognition of The Deteriorating Patient - NEWS2 (National Early Warning Scores) and Recognition of Sepsis. Mersey Care NHS Foundation Trust. 2018;4:1–39
30. Asafu A, Gall A. Letter to the Royal College of Physicians Regarding the Suitability of the National Early Warning Score in the Assessment of the Unwell Spinal Cord Injury Patient. Clin Med (Lond). 2015;15:406-7.
31. Drifte G, Siegrist ID, Tissieres P, Pugin J. Innate Immune Functions of Immature Neutrophils in Patients With Sepsis and Severe Systemic Inflammatory Response Syndrome. Crit Care Med. 2013;41(3):820-832.
32. Saboohi E, Saeed F, Khan RN, Khan MA. Immature to Total Neutrophil Ratio as an Early Indicator of Early Neonatal Sepsis. 2019;35(1):241-6.
33. Kheddar A, Chousterman BG, Guillou N, Barone S, Granjeaud S, Vallet H, et al. Two New Immature and Dysfunctional Neutrophil Cell Subsets Define a Predictive Signature of Sepsis Useable in Clinical Practice. BioRxiv. 2020.
34. Pfister D, Siegemund M, Dell-Kuster S, Smielewski P, Ruegg S, Strebel SP, et al. Cerebral Perfusion in Sepsis Associated Delirium. Crit Care. 2008;12(R63):1-9.
35. Nguyen DN, Spapen H, Su F, Schiettecatte J, Shi L, Hachimi-Idrissi S, et al. Elevated Serum Levels of S-100β Protein and Neuron-Specific Enolase are Associated with Brain Injury in Patients with Severe Sepsis and Septic Shock. Crit Care Med. 2006;34(7):1967–74.
36. Nguyen DN, Huyghens L, Zhang H, Schiettecatte J, Smitz J,Vincent JL. Cortisol Is An Associated Risk Factor of Brain Dysfunction in Patients with Severe Sepsis and Septic Shock. Biomed Res Intern. 2014;1-7.
37. Wu L, Feng Q, Ai ML, Deng SY, Liu ZY, Huang L, et al. The Dynamic Change of Serum S100B Levels from Day 1 to Day 3 is More Associated with Sepsis Associated Encephalopathy. Scient Rep. 2020;10(1):1-10.
38. Routsi C, Stamataki E, Nanas S, Psachoilia C, Stathopoulos A, Koroneos A, et al. Increased Level of Serum S100B Protein in Critically Ill Patients without Brain Injury. Shock. 2006;26;20-4.
39. Duda I, Krzych L, Szypulka HJ, Kowalik JL. Serum Level of the S100B Protein and Neuron –Spesific Enolase are Associated with Mortality in Critically Ill Patients. Acta Biochim Pol. 2017;64(4):647-52.
40. Piazza O, Russo E, Cotena S, Esposito G, Tufano R. Elevated S100B Levels Do Not Correlate with the Severity of Encephalopathy During Sepsis. Brit J of Anaest. 2007;99(4):518-21.
41. Fujiya A, Nagasaki H, Seino Y, Okawa T, Kato J, Fukami A, et al. The Role of S100B in the Interaction Between Adipocytes and Macrophages. Obesity. 2010;22(2):371-9.
42. Gogos CA, Drosou E, Bassaris HP, Skoutelis A. Pro- versus Anti-inflammatory Cytokine Profile in Patients with Severe Sepsis: A Marker for Prognosis and Future Therapeutic Options. The J of Infect Dis. 2000;181:176-80.
43. Matsumoto H, Ogura H, Shimizu K, Ikeda M, Hirose T, Matsuura H, et al. The Clinical Importance of a Cytokine Network in the Acute Phase of Sepsis. Sci Rep. 2018;8:1-11.
44. Surbatovic M, Popovic N, Vojvodic D, Milosevic I, Acimovic G, Stojicic M, et al. Cytokine Profile in Severe Gram Positive And Gram Negative Abdominal Sepsis. Sci Rep. 2015;5(11355):1-12.
45. Chang JS, Chang CC, Chien EY, Lin AA, Shiuan TC, Bai CH, et al. Association Between Interleukin-1β and Interleukin-10 Concentration: A Cross Sectional Study in Young Adolescents in Taiwan. BMC Pediatr. 2013;13(123):1-10.
46. Barry JC, Shakibakho S, Durrer C, Simtvhouk S, Jawanda K, Cheung S, et al. Hyporesponsiveness to the Anti-Inflammatory Action of Interleukin-10 in Type 2 Diabetes. Sci Rep. 2016;6:1-9.
2. Fleischmann C, Scherag A, Adhikari NKJ, Hartog CS, Tsaganos T, Schlattmann P, et al. Assessment of Global Incidence and Mortality of Hospital-treated Sepsis, Current Estimates and Limitations. Am J Resp Crit Care Med. 2016; 193(3):259–72.
3. Álvaro-Meca A, Jiménez-Sousa MA, Micheloud D, Sánchez-Lopez A, Heredia-Rodríguez M, Tamayo E, et al. Epidemiological Trends of Sepsis In The Twenty-First Century (2000-2013): An Analysis of Incidence, Mortality, and Associated Costs in Spain. Pop Health Metr. 2018;16(4):1–11.
4. Thompson K, Venkatesh B, Finfer S. Sepsis and Septic Shock: Current Approaches to Management. Intern Med J. 2019;49(2):160–70.
5. Phua J, Koh Y, Du B, Tang YQ, Divatia J V, Tan CC, et al. Management of Severe Sepsis in Patients Admitted to Asian Intensive Care Units: Prospective Cohort Study. BMJ. 2011;1-11: 452-7.
6. Tambajong RN, Lalenoh DC, Kumaat L. Profil Penderita Sepsis di ICU RSUP Prof. Dr. R. D. Kandou Manado Periode Desember 2014 – November 2015. Jurnal e-Clinic. 2016;4(1).
7. Lee YS, Choi JW, Park YH, Chung C, Park D Il, Lee JE, et al. Evaluation of the efficacy of the National Early Warning Score in predicting in-hospital mortality via the risk stratification. J Crit Care. 2018;47:222–6.
8. Mellhammar L, Linder A, Tverring J, Christensson B, Boyd JH, et al. NEWS2 Is Superior to qSOFA in Detecting Sepsis with Organ Dysfunction in the Emergency Department. J of Clin Med. 2019; 8(1128): 1–13.
9. Churpek MM, Snyder A, Han X, Sokol S, Pettit N, Howell MD, et al. Quick sepsis-related organ failure assessment, systemic inflammatory response syndrome, and early warning scores for detecting clinical deterioration in infected patients outside the intensive care unit. Am J Resp Crit Care Med. 2010;195(7):906–11.
10. Bastiana, Aryati, Iriani Y. Immature to Total Neutrophil (I/T) Ratio Sebagai Penunjang Diagnosis Sepsis Neonatorum. Indonesian Journal of Clinical Pathology and Medical Laboratory, Majalah Patologi Klinik Indonesia dan Laboratorium Medik. 2010; 16(2):73-7.
11. Henriquez-Camacho C, Losa J. Biomarkers for sepsis. Bio Research Intern. 2014; 1-6.
12. Mahalini DS. Ensefalopati pada anak dengan sepsis. SINAS Sepsis Pada Anak dan Neonatus. Fakultas Kedokteran, Universitas Udayana/RSUP Sanglah. 2011.
13. Yardan T, Erenler AK, Baydin A, Aydin K, Cokluk C. Usefulness of S100B Protein in Neurological Disorders. J Pak Med Assoc. 2011; 61(3):276-81.
14. Sun B, Liu H, Nie S. S100B Protein in Serum is Elevated After Global Cerebral Ischemic Injury. World J Emerg Med. 2013; 4(3):165–8.
15. Donato R, Sorci G, Riuzzi F, Arcuri C, Bianchi R, Brozzi F, et al. S100B’s Double Life : Intracellular Regulator and Extracellular Signal. Biochimica et Biophysica Acta. 2009;1793(6):1008–22.
16. Lobo-silva D, Carriche GM, Castro AG, Roque S, Saraiva M. Balancing the Immune Response in the Brain : IL-10 and its regulation. J of Neuroinflammation. 2016;13:297:1–10.
17. Peñaloza HF, Schultz BM, Nieto PA, Salazar GA, Suazo I, Gonzalez PA, et al. Opposing Roles of IL-10 in Acute Bacterial Infection. Cytokine & Growth Factor Reviews. 2016; 951:1-14.
18. Kotfis K, Wittebole X, Jaschinski U, Violan JS, Kashyap R, Leone M, et al. A Worldwide Perspective of Sepsis Epidemiology and Survival According to Age: Observational Data the ICON Audit. Journal of Critical Care. 2019;51:122-32.
19. Zhou J, Qian C, Zhao M, Yu X, Kang Y, Ma X, et al. Epidemiology and Outcome of Severe Sepsis and Septic Shock in Intensive Care Units in Mainland China. PLOS ONE. 2014;9(9):1-8.
20. Martin S, Perez A, Aldecoa C. Sepsis and Immunosenescence in the Elderly Patient: A Review. Frontiers in Medicine. 2017;4(20):1-10.
21. Solana R, Tarazona R, Gayoso I, Lesur O, Dupuis G, Fulop T. Innate Immunosenescence: Effect of Aging on Cells and Receptors of The Innate Immune System in Humans. Seminars In Immunology. 2012;24:331-341.
22. Agarwal S, Busse PJ. Innate and Adaptive Immunosenescence. Ann Allergy Asthma Immunol. 2010;104:183-190.
23. Chen YJ, Chen FL, Chen JH, Wu MT, Pharmd, Chen YL, et al. Epidemiology of Sepsis in Taiwan. Medicine. 2019;98(20)1-6.
24. Sakr Y, Elia C, Mascia L, Barberis B, Cardelino S, Livigni S, et al. The Influence of Gender on The Epidemiology of and Outcome from Severe Sepsis. Crit Care. 2013;17(R50):1-9.
25. Novita C, Hernaningsih Y, Wardhani P, Veterini A. The Correlation between Leucocyte CD64, Immature Granulocyte and Presepsin with Procalcitonin in Bacterial Sepsis Patient. Bali Med J. 2019;8(2):327-32.
26. Purwanto D,Astrawinata D. Mekanisme Kompleks Sepsis dan Syok Septik. Journal Biomedik. 2018;10(3):143-151.
27. Nierhaus A, Klatte S, Linssen J, Eismann N, Wichmann D, Hedke J, et al. Revisiting the White Blood Cell Count: Immature Granulocytes Count as a Diagnostic Marker to Discriminate Between SIRS and Sepsis-a Prospective, Observational Study. BMC Immunology. 2013;14(8):1-8.
28. Liu VX, Lu Y, Carey K, Gilbert E, Afshar M, Akel M, et al. Comparison of Early Warning Scoring Systems for Hospitalized Patients with and without Infection at Risk for In-Hospital Mortality and Transfer to the Intensive Care Unit. JAMA Network Open. 2020;3(5):1-12.
29. Mc Quillan S, Gordon C, Jones L, Young D. Management and Recognition of The Deteriorating Patient - NEWS2 (National Early Warning Scores) and Recognition of Sepsis. Mersey Care NHS Foundation Trust. 2018;4:1–39
30. Asafu A, Gall A. Letter to the Royal College of Physicians Regarding the Suitability of the National Early Warning Score in the Assessment of the Unwell Spinal Cord Injury Patient. Clin Med (Lond). 2015;15:406-7.
31. Drifte G, Siegrist ID, Tissieres P, Pugin J. Innate Immune Functions of Immature Neutrophils in Patients With Sepsis and Severe Systemic Inflammatory Response Syndrome. Crit Care Med. 2013;41(3):820-832.
32. Saboohi E, Saeed F, Khan RN, Khan MA. Immature to Total Neutrophil Ratio as an Early Indicator of Early Neonatal Sepsis. 2019;35(1):241-6.
33. Kheddar A, Chousterman BG, Guillou N, Barone S, Granjeaud S, Vallet H, et al. Two New Immature and Dysfunctional Neutrophil Cell Subsets Define a Predictive Signature of Sepsis Useable in Clinical Practice. BioRxiv. 2020.
34. Pfister D, Siegemund M, Dell-Kuster S, Smielewski P, Ruegg S, Strebel SP, et al. Cerebral Perfusion in Sepsis Associated Delirium. Crit Care. 2008;12(R63):1-9.
35. Nguyen DN, Spapen H, Su F, Schiettecatte J, Shi L, Hachimi-Idrissi S, et al. Elevated Serum Levels of S-100β Protein and Neuron-Specific Enolase are Associated with Brain Injury in Patients with Severe Sepsis and Septic Shock. Crit Care Med. 2006;34(7):1967–74.
36. Nguyen DN, Huyghens L, Zhang H, Schiettecatte J, Smitz J,Vincent JL. Cortisol Is An Associated Risk Factor of Brain Dysfunction in Patients with Severe Sepsis and Septic Shock. Biomed Res Intern. 2014;1-7.
37. Wu L, Feng Q, Ai ML, Deng SY, Liu ZY, Huang L, et al. The Dynamic Change of Serum S100B Levels from Day 1 to Day 3 is More Associated with Sepsis Associated Encephalopathy. Scient Rep. 2020;10(1):1-10.
38. Routsi C, Stamataki E, Nanas S, Psachoilia C, Stathopoulos A, Koroneos A, et al. Increased Level of Serum S100B Protein in Critically Ill Patients without Brain Injury. Shock. 2006;26;20-4.
39. Duda I, Krzych L, Szypulka HJ, Kowalik JL. Serum Level of the S100B Protein and Neuron –Spesific Enolase are Associated with Mortality in Critically Ill Patients. Acta Biochim Pol. 2017;64(4):647-52.
40. Piazza O, Russo E, Cotena S, Esposito G, Tufano R. Elevated S100B Levels Do Not Correlate with the Severity of Encephalopathy During Sepsis. Brit J of Anaest. 2007;99(4):518-21.
41. Fujiya A, Nagasaki H, Seino Y, Okawa T, Kato J, Fukami A, et al. The Role of S100B in the Interaction Between Adipocytes and Macrophages. Obesity. 2010;22(2):371-9.
42. Gogos CA, Drosou E, Bassaris HP, Skoutelis A. Pro- versus Anti-inflammatory Cytokine Profile in Patients with Severe Sepsis: A Marker for Prognosis and Future Therapeutic Options. The J of Infect Dis. 2000;181:176-80.
43. Matsumoto H, Ogura H, Shimizu K, Ikeda M, Hirose T, Matsuura H, et al. The Clinical Importance of a Cytokine Network in the Acute Phase of Sepsis. Sci Rep. 2018;8:1-11.
44. Surbatovic M, Popovic N, Vojvodic D, Milosevic I, Acimovic G, Stojicic M, et al. Cytokine Profile in Severe Gram Positive And Gram Negative Abdominal Sepsis. Sci Rep. 2015;5(11355):1-12.
45. Chang JS, Chang CC, Chien EY, Lin AA, Shiuan TC, Bai CH, et al. Association Between Interleukin-1β and Interleukin-10 Concentration: A Cross Sectional Study in Young Adolescents in Taiwan. BMC Pediatr. 2013;13(123):1-10.
46. Barry JC, Shakibakho S, Durrer C, Simtvhouk S, Jawanda K, Cheung S, et al. Hyporesponsiveness to the Anti-Inflammatory Action of Interleukin-10 in Type 2 Diabetes. Sci Rep. 2016;6:1-9.
| Files | ||
| Issue | Vol 61 No 10 (2023) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/acta.v61i10.15658 | |
| Keywords | ||
| I/T ratio S100B Interleukin-10 National early warning score (NEWS2) Sepsis | ||
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How to Cite
1.
Lestari N, Suromo L, Hendrianingtyas M, Setyadi A, Retnoningrum D. Correlation Between I/T Ratio, S100B, Interleukin-10 Serum, and NEWS2 Score in Sepsis. Acta Med Iran. 2024;61(10):592-598.
