The connection between the level of interleukin-6 and the clinical course of acute pulmonary embolism

Main Article Content

V. I. Tseluyko
M. V. Kurinna

Abstract

The aim – to investigate the possible influence of the level of interleukin-6 (IL-6) on the clinical course and remodeling of the right ventricle (RV) in patients with acute pulmonary embolism (PE).
Materials and methods. 56 patients with a diagnosis of acute PE, confirmed by сomputed tomographic pulmonary angiography (CTPA), and in whom the level of IL-6 was determined, were studied. The patients were divided into two groups: 1 group with a normal IL-6 level (less than 5.9 pg/ml), 2 group with an elevated IL-6 level (more than 5.9 pg/ml). Clinical and anamnestic and laboratory-instrumental data were analyzed, statistical analysis of the resulting figures was carried out.
Results and discussion. When comparing the groups depending on the level of IL-6, it was found that in group 1, not a single case of high-risk PE was recorded (p=0.052), while there was a significantly higher percentage of moderate-low-risk patients, p<0.05. Patients in group 2 had a higher heart rate (p=0.0006), lower SBP (p=0.04) at admission, and a tendency to increase body mass index (p=0.089). In addition, in group 2, the average levels of leukocytes (p=0.046), d-dimer (p=0.007), CRP (p=0.004) were higher, and the level of lymphocytes (p=0.008) was lower than in group 1, and the trend was determined to an increase in neutrophils (p=0.07) and CPK MB (p=0.89) in the 2nd group. According to the ultrasound data, in group 2 there was more often the detection of thrombosis of the veins of the lower extremities (p=0.003), a significantly larger size of the RV (p=0.02), a tendency to increase the size of the right atrium (RA) and a higher level of systolic pulmonary pressure (p=0.068 ). Analysis of the CTPA showed a greater dilatation of the left LA (p=0.0297) and an increase in the LV/LV index (p=0.0072) in the 2nd group. Correlation analysis revealed an inverse connection with the level of SpO2 (p=0.03) and lymphocytes (p=0.0065), a direct connection with heart rate (p<0.001), the ratio of LV/LV index (p=0.046), with the level of troponin I (p=0.014), D-dimer (p=0.026), leukocytes (p=0.026), neutrophils (0.038) and glucose (0.016), as well as the trend regarding the connection between the IL-6 level and the size of the RV according to echocardiography (p=0.07) and CPK MB level (p=0.086). The data of ROC analysis showed the connection of dilatation of the RV and Il-6 from the level of more than 7.65 pg/ml, with a sensitivity of the indicator of 90 %, specificity of 50 %.
Conclusions. An Il-6 level increase is more common in elderly patients, patients with venous thrombosis of the lower extremities, tachycardia, hypotension, and with a greater risk of an adverse course during the hospital period. In 2 groups, a higher level of other markers of inflammation (leukocytes, CRP), larger sizes of the RV, a higher level of pulmonary artery pressure according to echocardiography and values of RV/LV according to CTPA results are observed. A direct connection between IL-6 level and heart rate, troponin level, D-dimer level, LV/LV ratio and inverse connection with saturation and lymphocyte level was established according to correlation analysis. Multivariate regression analysis established an independent connection between the IL-6 level and some laboratory (CPK MB, blood glucose) and echocardiographic parameters (RA, LV ESD, LV EDV, LV ESV, LV EF). The threshold level of Il-6, which is accompanied by dilatation of the RV according to Roc-analysis data, was determined.

Article Details

Keywords:

pulmonary embolism, inflammation, interleukin-6, right ventricle remodeling.

References

Liu L, Li Y, Liu N, Luo J, Deng J, Peng W, Bai Y, Zhang G, Zhao G, Yan N, Li C, Long X. Establishment of machine learning-based tool for early detection of pulmonary embolism. Comput Methods Programs Biomed. 2024;244:107977. https://doi.org/10.1016/j.cmpb.2023.107977.

Falster C, Hellfritzsch M, Gaist TA, Brabrand M, Bhatnagar R, Nybo M, Andersen NH, Egholm G. Comparison of international guideline recommendations for the diagnosis of pulmonary embolism. The Lancet Haematology. 2023;10(11):e922-e935. https://doi.org/10.1016/S2352-3026(23)00181-3.

Janga C, Maligireddy AR, Aggarwal V, Klein AJ. Known Unknowns in the Contemporary Management of High-Risk Pulmonary Embolism: What Do the Guidelines Tell Us. Interventional Cardiology Clinics. Published online October 11, 2023. https://doi.org/10.1016/j.iccl.2023.08.003.

Cuomo JR, Arora V, Wilkins T. Management of Acute Pulmonary Embolism With a Pulmonary Embolism Response Team. J Am Board Fam Med. 2021;34(2):402-8. https://doi.org/10.3122/jabfm.2021.02.200308.

Saghazadeh A, Hafizi S, Rezaei N. Inflammation in venous thromboembolism: Cause or consequence? International Immunopharmacology. 2015;28(1):655-65. https://doi.org/10.1016/j.intimp.2015.07.044.

Branchford BR, Carpenter SL. The Role of Inflammation in Venous Thromboembolism. Front Pediatr. 2018;6:142. https://doi.org/10.3389/fped.2018.00142.

Jimenez D, Nieto R, Corres J, Fernández-Golfín C, Barrios D, Morillo R, Quezada CA, Huisman M, Yusen RD, Kline J. Diclofenac for reversal of right ventricular dysfunction in acute normotensive pulmonary embolism: A pilot study. Thrombosis Research. 2018;162:1-6. https://doi.org/10.1016/j.thromres.2017.12.002.

Ding J, Yue X, Tian X, Liao Z, Meng R, Zou M. Association between inflammatory biomarkers and venous thromboembolism: a systematic review and meta-analysis. Thrombosis J. 2023;21(1):82. https://doi.org/10.1186/s12959-023-00526-y.

Mukhopadhyay S, Johnson TA, Duru N, Buzza MS, Pawar NR, Sarkar R, Antalis TM. Fibrinolysis and Inflammation in Venous Thrombus Resolution. Front Immunol. 2019;10:1348. https://doi.org/10.3389/fimmu.2019.01348.

Lentz SR. Thrombosis in the setting of obesity or inflammatory bowel disease. Blood. 2016;128(20):2388-94. https://doi.org/10.1182/blood-2016-05-716720.

Lv X, Gao X, Liu J, Deng Y, Nie Q, Fan X, Ye Z, Liu P, Wen J. Immune-mediated inflammatory diseases and risk of venous thromboembolism: A Mendelian randomization study. Front Immunol. 2022;13:1042751. https://doi.org/10.3389/fimmu.2022.1042751.

Iwadate K, Tanno K, Doi M, Takatori T, Ito Y. Two cases of right ventricular ischemic injury due to massive pulmonary embolism. Forensic Sci Int. 2001;116(2-3):189-95. https://doi.org/10.1016/s0379-0738(00)00367-4.

Sydykov A, Mamazhakypov A, Petrovic A, Kosanovic D, Sarybaev AS, Weissmann N, Ghofrani HA, Schermuly RT. Inflammatory Mediators Drive Adverse Right Ventricular Remodeling and Dysfunction and Serve as Potential Biomarkers. Front Physiol. 2018;9:609. https://doi.org/10.3389/fphys.2018.00609.

Van Aken BE, den Heijer M, Bos GM, van Deventer SJ, Reitsma PH. Recurrent venous thrombosis and markers of inflammation. Thromb Haemost. 2000;83(4):536-9.

Musil D. Acute infections, venous thrombosis, and recommended thromboprophylaxis. Vnitr Lek. 2020;66(8):17-23.

Folsom AR, Lutsey PL, Astor BC, Cushman M. C-reactive protein and venous thromboembolism. A prospective investigation in the ARIC cohort. Thromb Haemost. 2009;102(4):615-9. https://doi.org/10.1160/TH09-04-0274.

Galeano-Valle F, Ordieres-Ortega L, Oblitas CM, Del-Toro-Cervera J, Alvarez-Sala-Walther L, Demelo-Rodríguez P. Inflammatory Biomarkers in the Short-Term Prognosis of Venous Thromboembolism: A Narrative Review. Int J Mol Sci. 2021;22(5):2627. https://doi.org/10.3390/ijms22052627.

Kantarcioglu B, Darki A, Siddiqui F, Krupa E, Vural M, Kacmaz M, Hoppensteadt D, Iqbal O, Jeske W, Walenga J, Adiguzel C, Fareed J. Predictive Role of Blood Cellular Indices and Their Relationship with Endogenous Glycosaminoglycans as Determinants of Inflammatory Biomarkers in Pulmonary Embolism. Clin Appl Thromb Hemost. 2022;28:10760296221104800. https://doi.org/10.1177/10760296221104801.

Omar HR, Mirsaeidi M, Rashad R, Hassaballa H, Enten G, Helal E, Mangar D, Camporesi EM.Association of Serum Albumin and Severity of Pulmonary Embolism. Medicina (Kaunas). 2020;56(1):26. https://doi.org/10.3390/medicina56010026.

Purdy JC, Shatzel JJ. The Hematologic Consequences of Obesity. Eur J Haematol. 2021;106(3):306-19. https://doi.org/10.1111/ejh.13560.

Tanaka T, Narazaki M, Kishimoto T. IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol. 2014;6(10):a016295. https://doi.org/10.1101/cshperspect.a016295.

Konstantinides SV, Meyer G, Becattini C, Bueno H, Geersing GJ, Harjola VP, Huisman MV, Humbert M, Jennings CS, Jiménez D, Kucher N, Lang IM, Lankeit M, Lorusso R, Mazzolai L, Meneveau N, Ní Áinle F, Prandoni P, Pruszczyk P, Righini M, Torbicki A, Van Belle E, Zamorano JL 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. 2020;41(4):543-603. https://doi.org/10.1093/eurheartj/ehz405.

Bikdeli B, Lobo JL, Jiménez D, Green P, Fernández-Capitán C, Bura-Riviere A, Otero R, DiTullio MR, Galindo S, Ellis M, Parikh SA, Monreal M. Early Use of Echocardiography in Patients With Acute Pulmonary Embolism: Findings From the RIETE Registry. J Am Heart Assoc. 2018;7(17):e009042. https://doi.org/10.1161/JAHA.118.009042.

Wang Y, Yu D, Yu Y, Liu X, Hu L, Gu Y. Association Between Inflammatory Mediators and Pulmonary Blood Flow in a Rabbit Model of Acute Pulmonary Embolism Combined With Shock. Front Physiol. 2020;11:1051. https://doi.org/10.3389/fphys.2020.01051.

Mahemuti A, Abudureheman K, Aihemaiti X, Hu XM, Xia YN, Tang BP, Upur H. Association of interleukin-6 and C-reactive protein genetic polymorphisms levels with venous thromboembolism. Chin Med J (Engl). 2012;125(22):3997-4002.

Tseluyko VY, Yakovleva LM, Sukhova SM. The short - term prognosis and gender characteristics of clinical manifestation of the pulmonary embolism. Emergency Medicine. 2016;(6.77):102-10. https://doi.org/10.22141/2224-0586.6.77.2016.82175. Ukrainian.

Chen YL, Wright C, Pietropaoli AP, Elbadawi A, Delehanty J, Barrus B, Gosev I, Trawick D, Patel D, Cameron SJ. Right ventricular dysfunction is superior and sufficient for risk stratification by a pulmonary embolism response team. J Thromb Thrombolysis. 2020;49(1):34-41. https://doi.org/10.1007/s11239-019-01922-w.

Prins KW, Archer SL, Pritzker M, Rose L, Weir EK, Sharma A, Thenappan T. Interleukin-6 is independently associated with right ventricular function in pulmonary arterial hypertension. J Heart Lung Transplant. 2018;37(3):376-84. https://doi.org/10.1016/j.healun.2017.08.011.

Most read articles by the same author(s)

1 2 > >>