Thromb Haemost 2002; 87(01): 42-46
DOI: 10.1055/s-0037-1612941
Review Article
Schattauer GmbH

The Role of Cytokines in Activation of Coagulation and Fibrinolysis in Dengue Shock Syndrome[*]

Catharina Suharti
1   Departments of Medicine and
,
Eric C.M. van Gorp
2   Department of Medicine, Slotervaart Hospital, Amsterdam
,
Tatty E. Setiati
3   Paediatrics, Faculty of Medicine, Diponegoro University and Dr. Kariadi Hospital, Semarang, Indonesia
,
Wil M.V. Dolmans
4   Department of Medicine, University Medical Centre St. Radboud, Nijmegen
,
Robert J. Djokomoeljanto
1   Departments of Medicine and
,
C. Erik Hack
5   Central Laboratory of The Netherlands Red Cross Blood Transfusion Service and Department Clinical Chemistry, Academic Hospital Vrije Universiteit, Amsterdam
,
Hugo ten Cate
6   Laboratory for Experimental Internal Medicine, Academic Medical Centre, Amsterdam, The Netherlands
,
Jos W.M. van der Meer
4   Department of Medicine, University Medical Centre St. Radboud, Nijmegen
› Author Affiliations
Further Information

Publication History

Received 12 June 2001

Accepted 01 October 2001

Publication Date:
13 December 2017 (online)

Summary

In a prospective clinical study of 50 patients with Dengue Shock Syndrome (DSS), we investigated the association of tumor necrosis factor-a (TNF-a), interleukin-1f3 (IL-1f3), IL-1 receptor antagonist (IL-1Ra), and IL-6 with activation markers of coagulation (F1+2 and TATc) and fibrinolysis (t-PA, PAPc, and D-dimer). We found that TNF-a, IL-1f3 and Il-1Ra, but not IL-6, concentrations were elevated in the circulation during the early stage of infection and at discharge from hospital. TNF-a was significantly associated with D-dimer, an activation marker of fibrinolysis (p < 0.003), but not with activation markers of coagulation. IL-1f3 was significantly associated with t-PA (p < 0.03). IL-1Ra was significantly associated with F1+2, TATc (p < 0.04 and p < 0.02, respectively), whereas IL-6 was significantly associated with both, activation markers of coagulation (F1+2; p < 0.03) and fibrinolysis (PAPc; p = 0.002). Our data are in line with studies in bacterial sepsis. In severe dengue virus infection the same cytokines are involved in the onset and regulation of hemostasis.

* Financial support: Royal Netherlands Academy of Arts and Sciences (KNAW).


 
  • References

  • 1 Van Gorp ECM, Suharti C, ten Cate H, Dolmans WMV, van der Meer JWM, ten Cate JW, Brandjes DPM. Infectious Diseases and Coagulation Disorders. J Infect Dis 1999; 180: 176-86.
  • 2 Osterud B, Flaegstad T. Increased tissue thromboplastin activity in monocytes of patients with meningococcal infections related to unfavourable prognosis. Thromb Haemost 1983; 49: 5-7.
  • 3 Voss R, Matthias FR, Borkowski G, Reitz D. Activation and inhibition of fibrinolysis in septic patients in an internal intensive care unit. B J Haematol 1990; 75: 99-105.
  • 4 Brandtzaeg P, Joo GB, Brusletto B, Kierulf P. Plasminogen activator inhibitor 1 and 2, and a2-antiplasmin, and endotoxin levels in systemic meningococcal disease. Thromb Res 1990; 57: 271-78.
  • 5 Van Deventer SJH, Büller HR, Ten Cate JW, Aarden LA, Hack CE, Sturk A. Experimental endotoxaemia in humans: analysis of cytokine release and coagulation, fibrinolytic and complement pathways. Blood 1990; 76: 2520-26.
  • 6 Suffredini AF, Harpel PC, Parrillo JE. Promotion and subsequent inhibition of plasminogen activator after administration of intravenous endotoxin to normal subjects. N Engl J Med 1989; 320: 1165-72.
  • 7 Van der Poll T, Büller HR, Ten Cate H, Wortel CH, Bauer KA, van Deventer SJH, Hack CE, Sauerwein HP, Rosenberg RD, ten Cate JW. Activation of coagulation after administration of tumor necrosis factor in healthy subjects. N Engl J Med 1990; 322: 1622-27.
  • 8 Van der Poll T, Levi M, Büller HR, van Deventer SJH, de Boer JP, Hack CE, ten Cate JW. Fibrinolytic response to tumor necrosis factor in healthy subjects. J Exp Med 1991; 174: 729-32.
  • 9 Jansen PM, Boermeester MA, Fischer E, de Jong IW, van der Poll T, Moldawer LL, Hack CE, Lowry SF. Contribution of interleukin-1 to activation of coagulation and fibrinolysis, to neutrophil degranulation and the release of sPLA2 in sepsis Studies in non-human primates following interleukin-1a administration and during lethal bacteremia. Blood 1995; 86: 1027-34.
  • 10 Boermeester MA, van Leeuwen PAM, Coyle SM, Houdijk AJP, Eerenberg AM, Wolbink GJ, Pribble JP, Stiles DM, Wesdorp RIC, Hack CE, Lowry SF. Interleukin-1 receptor blockade in patients with sepsis syndrome: evidence that interleukin-1 contributes to the release of interleukin-6, elastase and phospholipase A2, and to the activation of the complement, coagulation and fibrinolytic system. Arch Surg 1995; 130: 739-48.
  • 11 Dengue haemorrhagic fever: diagnosis, treatment. prevention and control. 2d ed. Geneva: World Health Organization; 1997: 12-47.
  • 12 Dengue and dengue hemorrhagic fever in the Americas: guidlines for prevention and control. Washington, DC: Pan American Health Organization Sci Publ; 1994: 3-21.
  • 13 Bhamarapravati N. Pathology of dengue infections. In: Dengue and dengue hemorrhagic fever. Gubler DJ, Kuno G. eds. Wallingford, UK: Cab International; 1997: 115-32.
  • 14 Nimmannitya S. Dengue hemorrhagic fever: diagnosis and management. In: Dengue and dengue hemorrhagic fever. Gubler DJ, Kuno G. eds. Wallingford, UK: Cab International; 1997: 133-45.
  • 15 Halstead SB, O’Rourke EJ. Dengue viruses and mononuclear phagocytes I. Infection enhancement by non-neutralizing antibody. J Exp Med 1977; 146: 201-17.
  • 16 Kurane I, Rothman AL, Livingstone PG, Green S, Gagnon SJ, Janus J, Innis BL, Nimmannitya S, Nisalak A, Ennis FA. Immunopathologic mechanisms of dengue hemorrhagic fever and dengue shock syndrome. Arch Virol (Suppl) 1994; 09: 59-64.
  • 17 Jarvis C. Physical examination and health assessment. Philadelphia: WB Saunders; 1993: 178.
  • 18 Rigau-Perez JG, Clark GG, Gubler DJ, Reiter P, Sanders EJ, Vorndam AV. Dengue and dengue hemorrhagic fever. Lancet 1998; 352: 971-77.
  • 19 Sharp TW, Wallace MR, Hayes CG, Sanchez JL, DeFraites RF, Arthur RR, Thornton SA, Batchelor RA, Rozmajzl PJ, Hanson RK, Wu SJ, Iriye C, Burans JP. Dengue fever in U.S troops during operation restore hope, Somalia, 1992-1993. Am J Trop Med Hyg 1995; 53: 89-94.
  • 20 Innis BL, Nisalak A, Nimmannitya S, Kusalerdcharya S, Chongswasdi V, Suntayakorn S, Puttisri P, Hoke CH. An enzyme-linked immunosorbent assay to characterize dengue infections where dengue and Japanese Encephalitis co-circulate. Am J Trop Med Hyg 1989; 40: 418-27.
  • 21 Ruechusatsawat K, Morita K, Tanaka M, Vongcheree S, Rojanasuphot S, Warachit P, Kanai K, Thongtradol P, Nimnakorn M, Kanungkid S, Igarashi A. Daily observation of antibody levels among dengue patients detected by enzyme-linked immunosorbent assay (ELISA). Jpn J Trop Med Hyg 1984; 22: 9-12.
  • 22 Drenth JP, van Uum SH, van Deuren M, Pesman GJ, van der VenJongekrijg J, van der Meer JWM. Endurance run increases circulating IL-6 and IL-1Ra but downregulates ex-vivo TNF-alpha and IL-1beta production. J Appl Physiol 1995; 79: 1497-03.
  • 23 De Boer JP, Creasy AA, Chang A, Roem D, Brouwer MC, Eerenberg AJ, Hack CE, Taylor Jr FB. Activation patterns of coagulation and fibrinolysis in baboons following infusion with lethal or sublethal dose of Escherichia coli. Circ Shock 1993; 39: 59-67.
  • 24 Levi M, de Boer JP, Roem D, ten Cate JW, Hack CE. Plasminogen activation in vivo upon intravenous infusion of DDAVP Quantitative assessment of plasmin-alpha-2 antiplasmin complex with a novel monoclonal antibody based radioimmunoassay. Thromb Haemost 1992; 67: 111-16.
  • 25 Groen J, Velzing J, Copra C, Balentien E, Deubel V, Vorndam V, Osterhaus ADME. Diagnostic value of dengue virus-specific IgA and IgM serum antibody detection. Microbes and infection 1999; 01: 1-6.
  • 26 Van der Poll T, Levi M, Van Deventer SJH, Ten Cate H, Haagmans BL, Biemond BJ, Büller HR, Hack CE, Ten Cate JW. Differential effects of anti-tumor necrosis factor monoclonal antibodies on systemic inflammatory responses in experimental endotoxaemia in chimpanzees. Blood 1994; 83: 446-51.
  • 27 Van der Poll T, Coyle SM, Levi M, Jansen PM, Dentener M, Barbosa K, Buurman WA, Hack CE, ten Cate JW, Agosti JM, Lowry SF. Effect of recombinant dimeric tumor necrosis factor receptor on inflammatory responses to intravenous endotoxin in normal humans. Blood 1997; 89: 3727-34.
  • 28 Hinshaw LB, Tekamp-Olson P, Chang ACK, Lee PA, Taylor Jr FB, Murray CK, Peer GT, Emerson Jr TE, Passey B, Kuo GC. Survival of primates in LD100 septic shock following therapy with antibody to tumor necrosis factor (TNF). Circ Shock 1990; 30: 279-92.
  • 29 Biemond BJ, Levi M, ten Cate H, van der Poll T, Büller HR, Hack CE, ten Cate JW. Plasminogen activator and PAI-1 release during experimental endotoxaemia in chimpanzees; effects of various intervention in the cytokine and coagulation cascades. Clin Sci 1995; 88: 587-94.
  • 30 Stoudhardt JML, Levi M, Hack CE, Veenhof CHN, Romijn JA, Sauerwein HP, van der Poll T. Interleukin-6 stimulates coagulation, not fibrinolysis, in humans. Thromb Haemost 1996; 76: 738-42.