IL‑18 and IL‑35 in the serum of patients with sepsis thrombocytopenia and the clinical significance

Zhu,Meirong; Rong,Xiaoqian; Li,Min; Wang,Shaoqin

doi:10.3892/etm.2019.8347

IL‑18 and IL‑35 in the serum of patients with sepsis thrombocytopenia and the clinical significance

Authors:
- Meirong Zhu
- Xiaoqian Rong
- Min Li
- Shaoqin Wang
View Affiliations

Affiliations: Department of Critical Care Medicine, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, P.R. China
Published online on: December 18, 2019 https://doi.org/10.3892/etm.2019.8347
Pages: 1251-1258
Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Expression levels of interleukin‑18 (IL‑18) and IL‑35 in the serum of patients with sepsis and without thrombocytopenia and patients with sepsis thrombocytopenia (TCP) were detected to preliminarily investigate their clinical significance. One hundred and sixty‑six patients admitted to Jinan Central Hospital Affiliated to Shandong University from July 2013 to September 2015 were retrospectively analysed. There were 96 patients with sepsis without thrombocytopenia in the sepsis group, and 70 patients with sepsis TCP in the sepsis TCP group. In the same period, 80 healthy subjects were selected as the control group. Fluorescent quantitative PCR was used for the detection the expression of mRNA levels of IL‑18 and IL‑35, and Enzyme‑linked immunosorbent assay for the detection of the protein concentrations of IL‑18 and IL‑35 in the serum of peripheral blood. The correlation between IL‑18, IL‑35 and platelets was analyzed. There were significant differences in albumin, creatinine, total bilirubin and platelet count between the sepsis group and the sepsis TCP group (P<0.05); the expression levels of mRNA of IL‑18 and IL‑35 in a karyocyte in peripheral blood in the sepsis group and the sepsis TCP group were higher than those in the control group (P<0.05); the expression of mRNA of IL‑18 and IL‑35 in the sepsis TCP group was higher than those in the sepsis group (P<0.05). The concentration of IL‑18 and IL‑35 in the sepsis TCP group was higher than in the sepsis group (P<0.05); IL‑18 and IL‑35 were negatively correlated with platelets (r=‑0.8749, ‑0.6228, P<0.001). There was a significant positive correlation between serum IL‑18 and IL‑35 in the control group, sepsis group, and sepsis TCP group (r=0.5124, 0.5718, 0.5511, P<0.001). IL‑18 and IL‑35 were negatively correlated with the reduced degree of platelets in patients with sepsis and are likely to play an important role in the pathogenetic process of sepsis TCP.

View Figures

View References

1	Dewitte A, Lepreux S, Villeneuve J, Rigothier C, Combe C, Ouattara A and Ripoche J: Blood platelets and sepsis pathophysiology: A new therapeutic prospect in critically [corrected] ill patients? Ann Intensive Care. 7:1152017. View Article : Google Scholar : PubMed/NCBI
2	Fleischmann C, Scherag A, Adhikari NK, Hartog CS, Tsaganos T, Schlattmann P, Angus DC and Reinhart K; International Forum of Acute Care Trialists, : Assessment of global incidence and mortality of hospital-treated sepsis. Current estimates and limitations. Am J Respir Crit Care Med. 193:259–272. 2016. View Article : Google Scholar : PubMed/NCBI
3	Larkin CM, Santos-Martinez MJ, Ryan T and Radomski MW: Sepsis-associated thrombocytopenia. Thromb Res. 141:11–16. 2016. View Article : Google Scholar : PubMed/NCBI
4	Yaguchi A, Lobo FL, Vincent JL and Pradier O: Platelet function in sepsis. J Thromb Haemost. 2:2096–2102. 2004. View Article : Google Scholar : PubMed/NCBI
5	Vandijck DM, Blot SI, De Waele JJ, Hoste EA, Vandewoude KH and Decruyenaere JM: Thrombocytopenia and outcome in critically ill patients with bloodstream infection. Heart Lung. 39:21–26. 2010. View Article : Google Scholar : PubMed/NCBI
6	Xu R, Lin F, Bao C, Huang H, Ji C, Wang S, Jin L, Sun L, Li K, Zhang Z, et al: Complement 5a receptor-mediated neutrophil dysfunction is associated with a poor outcome in sepsis. Cell Mol Immunol. 13:103–109. 2016. View Article : Google Scholar : PubMed/NCBI
7	Li MF, Li XL, Fan KL, Yu YY, Gong J, Geng SY, Liang YF, Huang L, Qiu JH, Tian XH, et al: Platelet desialylation is a novel mechanism and a therapeutic target in thrombocytopenia during sepsis: An open-label, multicenter, randomized controlled trial. J Hematol Oncol. 10:1042017. View Article : Google Scholar : PubMed/NCBI
8	Yeaman MR and Bayer AS: Staphylococcus aureus, platelets, and the heart. Curr Infect Dis Rep. 2:281–298. 2000. View Article : Google Scholar : PubMed/NCBI
9	Claushuis TA, van Vught LA, Scicluna BP, Wiewel MA, Klein Klouwenberg PM, Hoogendijk AJ, Ong DS, Cremer OL, Horn J, Franitza M, et al Molecular Diagnosis and Risk Stratification of Sepsis Consortium, : Thrombocytopenia is associated with a dysregulated host response in critically ill sepsis patients. Blood. 127:3062–3072. 2016. View Article : Google Scholar : PubMed/NCBI
10	Kwak A, Lee Y, Kim H and Kim S: Intracellular interleukin (IL)-1 family cytokine processing enzyme. Arch Pharm Res. 39:1556–1564. 2016. View Article : Google Scholar : PubMed/NCBI
11	Eidt MV, Nunes FB, Pedrazza L, Caeran G, Pellegrin G, Melo DA, Possuelo L, Jost RT, Dias HB, Donadio MV, et al: Biochemical and inflammatory aspects in patients with severe sepsis and septic shock: The predictive role of IL-18 in mortality. Clin Chim Acta. 453:100–106. 2016. View Article : Google Scholar : PubMed/NCBI
12	Okuhara Y, Yokoe S, Iwasaku T, Eguchi A, Nishimura K, Li W, Oboshi M, Naito Y, Mano T, Asahi M, et al: Interleukin-18 gene deletion protects against sepsis-induced cardiac dysfunction by inhibiting PP2A activity. Int J Cardiol. 243:396–403. 2017. View Article : Google Scholar : PubMed/NCBI
13	Li M, Eckl J, Geiger C, Schendel DJ and Pohla H: A novel and effective method to generate human porcine-specific regulatory T cells with high expression of IL-10, TGF-β1 and IL-35. Sci Rep. 7:39742017. View Article : Google Scholar : PubMed/NCBI
14	Gao P, Su Z, Lv X and Zhang J: Interleukin-35 in asthma and its potential as an effective therapeutic agent. Mediators Inflamm. 2017:59318652017. View Article : Google Scholar : PubMed/NCBI
15	Sha X, Meng S, Li X, Xi H, Maddaloni M, Pascual DW, Shan H, Jiang X, Wang H and Yang XF: Interleukin-35 inhibits endothelial cell activation by suppressing MAPK-AP-1 pathway. J Biol Chem. 290:19307–19318. 2015. View Article : Google Scholar : PubMed/NCBI
16	Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL and Ramsay G; SCCM/ESICM/ACCP/ATS/SIS, : 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 31:1250–1256. 2003. View Article : Google Scholar : PubMed/NCBI
17	Vardas K, Apostolou K, Briassouli E, Goukos D, Psarra K, Botoula E, Tsagarakis S, Magira E, Routsi C, Nanas S, et al: Early response roles for prolactin cortisol and circulating and cellular levels of heat shock proteins 72 and 90α in severe sepsis and SIRS. BioMed Res Int. 2014:8035612014. View Article : Google Scholar : PubMed/NCBI
18	Tang G, Wang XM, Meng JX, Luan CL, Chen JF, Wu YQ, Zhang XN and He ZY: Efficacy of recombinant human thrombopoietin and recombinant human interleukin 11 for treatment of chemotherapy induced thrombocytopenia in acute myeloid leukaemia patients. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 26:234–238. 2018.(In Chinese). PubMed/NCBI
19	Semple JW and Freedman J: Platelets and innate immunity. Cell Mol Life Sci. 67:499–511. 2010. View Article : Google Scholar : PubMed/NCBI
20	Yeaman MR: Platelets in defense against bacterial pathogens. Cell Mol Life Sci. 67:525–544. 2010. View Article : Google Scholar : PubMed/NCBI
21	Yan Y, Jiang W, Liu L, Wang X, Ding C, Tian Z and Zhou R: Dopamine controls systemic inflammation through inhibition of NLRP3 inflammasome. Cell. 160:62–73. 2015. View Article : Google Scholar : PubMed/NCBI
22	Cui YL, Wang B, Gao HM, Xing YH, Li J, Li HJ, Lin Z and Wang YQ: Interleukin-18 and miR-130a in severe sepsis patients with thrombocytopenia. Patient Prefer Adherence. 10:313–319. 2016. View Article : Google Scholar : PubMed/NCBI
23	Vignali DA and Kuchroo VK: IL-12 family cytokines: Immunological playmakers. Nat Immunol. 13:722–728. 2012. View Article : Google Scholar : PubMed/NCBI
24	Kochetkova I, Golden S, Holderness K, Callis G and Pascual DW: IL-35 stimulation of CD39+ regulatory T cells confers protection against collagen II-induced arthritis via the production of IL-10. J Immunol. 184:7144–7153. 2010. View Article : Google Scholar : PubMed/NCBI
25	Du WX, He Y, Jiang HY, Ai Q and Yu JL: Interleukin 35: A novel candidate biomarker to diagnose early onset sepsis in neonates. Clin Chim Acta. 462:90–95. 2016. View Article : Google Scholar : PubMed/NCBI
26	Oberholzer A, Steckholzer U, Kurimoto M, Trentz O and Ertel W: Interleukin-18 plasma levels are increased in patients with sepsis compared to severely injured patients. Shock. 16:411–414. 2001. View Article : Google Scholar : PubMed/NCBI
27	Sun RQ and Zhang SL: The value of serum interleukin-18 and 10 in the evaluation of severity and prognosis in the early stage of sepsis. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 23:299–301. 2011.(In Chinese). PubMed/NCBI
28	Emmanuilidis K, Weighardt H, Matevossian E, Heidecke CD, Ulm K, Bartels H, Siewert JR and Holzmann B: Differential regulation of systemic IL-18 and IL-12 release during postoperative sepsis: High serum IL-18 as an early predictive indicator of lethal outcome. Shock. 18:301–305. 2002. View Article : Google Scholar : PubMed/NCBI
29	Lally KP, Cruz E and Xue H: The role of anti-tumor necrosis factor-alpha and interleukin-10 in protecting murine neonates from Escherichia coli sepsis. J Pediatr Surg. 35:852–855. 2000. View Article : Google Scholar : PubMed/NCBI
30	Zhao HQ, Li WM, Lu ZQ, Sheng ZY and Yao YM: The growing spectrum of anti-inflammatory interleukins and their potential roles in the development of sepsis. J Interferon Cytokine Res. 35:242–251. 2015. View Article : Google Scholar : PubMed/NCBI
31	Shaheen IA, Botros SKA and Morgan DS: Detection of expression of IL-18 and its binding protein in Egyptian pediatric immune thrombocytopenic purpura. Platelets. 25:193–196. 2014. View Article : Google Scholar : PubMed/NCBI
32	Cao J, Xu F, Lin S, Tao X, Xiang Y, Lai X and Zhang L: IL-35 is elevated in clinical and experimental sepsis and mediates inflammation. Clin Immunol. 161:89–95. 2015. View Article : Google Scholar : PubMed/NCBI