Volume 77, Issue 2
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


Tumor necrosis factor-α (TNF-α) and soluble TNF receptors (sTNFR1 and sTNFR2) have been implicated in infectious diseases. We investigated dynamic changes among TNF-α, membrane TNF receptors (mTNFR1 and mTNFR2), and sTNFR1 and sTNFR2 levels for patients with dengue hemorrhagic fever (DHF) and those not infected during a DEN-2 outbreak in southern Taiwan in 2002–2003. Patients with DHF showed the lowest levels of mTNFR1 and mTNFR2 expression. Multivariate analysis showed that a decrease in levels of mTNFR1 expression was the only factor significantly different between patients with DHF and those with dengue fever. Moreover, lower mTNFR1 expression was significantly correlated with higher plasma TNF-α levels, but not with sTNFR1 levels in patients with DHF. This finding suggests that a lower level of mTNFR1 expression in response to a higher plasma TNF-α level may be a pathogenic marker for early detection of DHF.


Article metrics loading...

The graphs shown below represent data from March 2017
Loading full text...

Full text loading...



  1. Monath TP, 1994. Dengue: the risk to developed and developing countries. Proc Natl Acad Sci U S A 91 : 2395–2400. [Google Scholar]
  2. Lei HY, Yeh TM, Liu HS, Lin YS, Chen SH, Liu CC, 2001. Immunopathogenesis of dengue virus infection. J Biomed Sci 8 : 377–388. [Google Scholar]
  3. Mackenzie JS, Chua KB, Daniels PW, Eaton BT, Field HE, Hall RA, Halpin K, Johansen CA, Kirkland PD, Lam SK, McMinn P, Nisbet DJ, Paru R, Pyke AT, Ritchie SA, Siba P, Smith DW, Smith GA, van den Hurk AF, Wang LF, Williams DT, 2001. Emerging viral diseases of southeast Asia and the western Pacific. Emerg Infect Dis 7 : 497–504. [Google Scholar]
  4. Hober D, Shen L, Benyoucef S, de Groote D, Deubel V, Wattre P, 1996. Enhanced TNF alpha production by monocytic-like cells exposed to dengue virus antigens. Immunol Lett 53 : 115–120. [Google Scholar]
  5. Yang KD, Lee CS, Hwang KP, Chu ML, Shaio MF, 1995. A model to study cytokine profiles in primary and heterologously secondary dengue-2 virus infections. Acta Virol 39 : 19–21. [Google Scholar]
  6. Anderson R, Wang S, Osiowy C, Issekutz AC, 1997. Activation of endothelial cells via antibody-enhanced dengue virus infection of peripheral blood monocytes. J Virol 71 : 4226–4232. [Google Scholar]
  7. Herbein G, O’Brien WA, 2000. Tumor necrosis factor (TNF)-alpha and TNF receptors in viral pathogenesis. Proc Soc Exp Biol Med 223 : 241–257. [Google Scholar]
  8. Hober D, Poli L, Roblin B, Gestas P, Chungue E, Granic G, Imbert P, Pecarere JL, Vergez-Pascal R, Wattre P, 1993. Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-1 beta (IL-1 beta) in dengue-infected patients. Am J Trop Med Hyg 48 : 324–331. [Google Scholar]
  9. Vandenabeele P, Declercq W, Beyaert R, Fiers W, 1995. Two tumour necrosis factor receptors: structure and function. Trends Cell Biol 5 : 392–399. [Google Scholar]
  10. Chen LC, Lei HY, Liu CC, Shiesh SC, Chen SH, Liu HS, Lin YS, Wang ST, Shyu HW, Yeh TM, 2006. Correlation of serum levels of macrophage migration inhibitory factor with disease severity and clinical outcome in dengue patients. Am J Trop Med Hyg 74 : 142–147. [Google Scholar]
  11. Braga EL, Moura P, Pinto LM, Ignacio SR, Oliveira MJ, Cordeiro MT, Kubelka CF, 2001. Detection of circulant tumor necrosis factor-alpha, soluble tumor necrosis factor p75 and interferon-gamma in Brazilian patients with dengue fever and dengue hemorrhagic fever. Mem Inst Oswaldo Cruz 96 : 229–232. [Google Scholar]
  12. Pinto LM, Oliveira SA, Braga EL, Nogueira RM, Kubelka CF, 1999. Increased pro-inflammatory cytokines (TNF-alpha and IL-6) and anti-inflammatory compounds (sTNFRp55 and sTNFRp75) in Brazilian patients during exanthematic dengue fever. Mem Inst Oswaldo Cruz 94 : 387–394. [Google Scholar]
  13. Atrasheuskaya A, Petzelbauer P, Fredeking TM, Ignatyev G, 2003. Anti-TNF antibody treatment reduces mortality in experimental dengue virus infection. FEMS Immunol Med Microbiol 35 : 33–42. [Google Scholar]
  14. Eigler A, Sinha B, Hartmann G, Endres S, 1997. Taming TNF: strategies to restrain this proinflammatory cytokine. Immunol Today 18 : 487–492. [Google Scholar]
  15. Jablonska E, Jablonski J, Holownia A, 1999. Role of neutrophils in release of some cytokines and their soluble receptors. Immunol Lett 70 : 191–197. [Google Scholar]
  16. Khor BS, Liu JW, Lee IK, Yang KD, 2006. Dengue hemorrhagic fever patients with acute abdomen: clinical experience of 14 cases. Am J Trop Med Hyg 74 : 901–904. [Google Scholar]
  17. Lee IK, Liu JW, Yang KD, 2005. Clinical characteristics and risk factors for concurrent bacteremia in adults with dengue hemorrhagic fever. Am J Trop Med Hyg 72 : 221–226. [Google Scholar]
  18. Chen RF, Liu JW, Yeh WT, Wang L, Chang JC, Yu HR, Cheng JT, Yang KD, 2005. Altered T helper 1 reaction but not increase of virus load in patients with dengue hemorrhagic fever. FEMS Immunol Med Microbiol 44 : 43–50. [Google Scholar]
  19. Yang KD, Yeh WT, Yang MY, Chen RF, Shaio MF, 2001. Antibody-dependent enhancement of heterotypic dengue infections involved in suppression of IFNgamma production. J Med Virol 63 : 150–157. [Google Scholar]
  20. World Health Organization, 1997. Dengue Hemorrhage Fever: Diagnosis, Treatment, Prevention and Control. Geneva: World Health Organization.
  21. Yeh WT, Chen RF, Wang L, Liu JW, Shaio MF, Yang KD, 2006. Implications of previous subclinical dengue infection but not virus load in dengue hemorrhagic fever. FEMS Immunol Med Microbiol 48 : 84–90. [Google Scholar]
  22. Chen RF, Yeh WT, Yang MY, Yang KD, 2001. A model of the real-time correlation of viral titers with immune reactions in antibody-dependent enhancement of dengue-2 infections. FEMS Immunol Med Microbiol 30 : 1–7. [Google Scholar]
  23. Tain YL, Liu CA, Yang KD, 2002. Implications of blood soluble and cell surface tumor necrosis factor receptors in childhood nephrotic syndrome. Pediatr Nephrol 17 : 926–932. [Google Scholar]
  24. Liu CA, Wang CL, Wang FS, Huang HC, Chuang H, Chen RF, Tai FY, Yang KD, 2005. Higher spontaneous and TNFalpha-induced apoptosis of neonatal blood granulocytes. Pediatr Res 58 : 132–137. [Google Scholar]
  25. Hale KK, Smith CG, Baker SL, Vanderslice RW, Squires CH, Gleason TM, Tucker KK, Kohno T, Russell DA, 1995. Multi-functional regulation of the biological effects of TNF-alpha by the soluble type I and type II TNF receptors. Cytokine 7 : 26–38. [Google Scholar]
  26. Van Zee KJ, Kohno T, Fischer E, Rock CS, Moldawer LL, Lowry SF, 1992. Tumor necrosis factor soluble receptors circulate during experimental and clinical inflammation and can protect against excessive tumor necrosis factor alpha in vitro and in vivo. Proc Natl Acad Sci U S A 89 : 4845–4849. [Google Scholar]
  27. Higuchi M, Aggarwal BB, 1994. Differential roles of two types of the TNF receptor in TNF-induced cytotoxicity, DNA fragmentation, and differentiation. J Immunol 152 : 4017–4025. [Google Scholar]
  28. Pedron T, Girard R, Chaby R, 2003. TLR4-dependent lipopolysaccharide-induced shedding of tumor necrosis factor receptors in mouse bone marrow granulocytes. J Biol Chem 278 : 20555–20564. [Google Scholar]
  29. Dri P, Gasparini C, Menegazzi R, Cramer R, Alberi L, Presani G, Garbisa S, Patriarca P, 2000. TNF-Induced shedding of TNF receptors in human polymorphonuclear leukocytes: role of the 55-kDa TNF receptor and involvement of a membrane-bound and non-matrix metalloproteinase. J Immunol 165 : 2165–2172. [Google Scholar]
  30. Higuchi M, Aggarwal BB, 1994. TNF induces internalization of the p60 receptor and shedding of the p80 receptor. J Immunol 152 : 3550–3558. [Google Scholar]
  31. van der Poll T, Calvano SE, Kumar A, Braxton CC, Coyle SM, Barbosa K, Moldawer LL, Lowry SF, 1995. Endotoxin induces downregulation of tumor necrosis factor receptors on circulating monocytes and granulocytes in humans. Blood 86 : 2754–2759. [Google Scholar]
  32. Schleiffenbaum B, Fehr J, 1990. The tumor necrosis factor receptor and human neutrophil function. Deactivation and cross-deactivation of tumor necrosis factor-induced neutrophil responses by receptor down-regulation. J Clin Invest 86 : 184–195. [Google Scholar]
  33. Schleiffenbaum B, Olgiati L, Fehr J, 1992. TNF-specific deactivation of granulocytes in vivo: a possible mechanism of self-protection. Eur J Haematol 49 : 239–245. [Google Scholar]

Data & Media loading...

  • Received : 13 Nov 2006
  • Accepted : 01 May 2007

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error