Pattern of serum cytokines in children with dengue hemorrhagic fever in Neiva, Colombia
##plugins.themes.bootstrap3.article.main##
Cytokines play a critical role in the pathogenesis of dengue hemorrhagic fever and have been used as markers of severity disease. In this study we measured serum levels of five cytokines in dengue infected children and correlate their levels with shock and complicated forms such as myocarditis, hepatitis or bleeding. Methods: 30 patients who met WHO criteria for dengue hemorrhagic fever (DHF) were enrolled and classified into two groups: group one without shock (grade I and II) and group two with shock (grade III and IV). Serum levels of TNFá, IL-6, IL-10, IL-4 and IFNã were measured by ELISA at first day of defervescence and were compared with serum levels of 28 healthy children. Results: from 30 patients, 9 were assigned to group number one (median age 67 months) and 21 to group two (median age 42 months). Statistical differences were found between dengue infected patients and controls: controls IL-6 (5.2 pg/ml), group 1 (485 pg/ml) (p=0.002) and group 2 (190 pg/ml) (p=0.001); TNFá, control group (70 pg/ml), group 1 (586.7 pg/ml) (p=0.021) and group 2 (320.7 pg/ml) (p<0.001) and for IFNã, control group (12.3 pg/ml), group 2 (27.5 pg/ml) (p=0.019). However, we could not find correlation between cytokines and shock or complicated forms of illness. IL-4 and IL-10 did not show differences between any tested groups. Conclusion: IL-6, TNFá and IFNã are elevated in children with dengue hemorrhagic fever, but there was not correlation with severe forms of shock.
Downloads
##plugins.themes.bootstrap3.article.details##
World Health Organization. Dengue guidelines for diagnosis, treatment, prevention and control: new edition. Geneva: World Health Organization; 2009.
Chaturvedi UC, Shrivastava R, Nagar R. Dengue vaccines: problems and prospects. Indian J Med Res 2005;121(5):639-652.
Instituto Nacional de Salud. Análisis epidemiológico semana 35. Boletín Epidemiológico Instituto Nacional de Salud. 2006.
Nimmannitya S, Thisyakorn U, Hemsrichart V. Dengue haemorrhagic fever with unusual manifestations. Southeast Asian J Trop Med Public Health 1987;18(3):398-406.
Solomon T, Dung NM, Vaughn DW, Kneen R, Thao LT, Raengsakulrach B, et al. Neurological manifestations of dengue infection. Lancet 2000;355(9209):1053-1059.
Kamath SR, Ranjit S. Clinical features, complications and atypical manifestations of children with severe forms of dengue hemorrhagic fever in South India. Indian J Pediatr 2006;73(10):889-895.
Chaturvedi UC. The curse of dengue. Indian J Med Res 2006;124(5):467-470.
Bosch I, Xhaja K, Estevez L, Raines G, Melichar H, Warke RV, et al. Increased production of interleukin-8 in primary human monocytes and in human epithelial and endothelial cell lines after dengue virus challenge. J Virol 2002;76(11):5588-5597.
Suharti C, van Gorp EC, Dolmans WM, Setiati TE, Hack CE, Djokomoeljanto R, et al. Cytokine patterns during dengue shock syndrome. Eur Cytokine Netw 2003;14(3):172-177.
Libraty DH, Pichyangkul S, Ajariyakhajorn C, Endy TP, Ennis FA. Human dendritic cells are activated by dengue virus infection: enhancement by gamma interferon and implications for disease pathogenesis. J Virol 2001;75(8):3501-3508.
Chen LC, Lei HY, Liu CC, Shiesh SC, Chen SH, Liu HS, et al. Correlation of serum levels of macrophage migration inhibitory factor with disease severity and clinical outcome in dengue patients. Am J Trop Med Hyg 2006;74(1):142-147.
Stephens HA, Klaythong R, Sirikong M, Vaughn DW, Green S, Kalayanarooj S, et al. HLA-A and -B allele associations with secondary dengue virus infections correlate with disease severity and the infecting viral serotype in ethnic Thais. Tissue Antigens 2002; 60(4):309-318.
Juffrie M, van Der Meer GM, Hack CE, Haasnoot K, Sutaryo, Veerman AJ, et al. Inflammatory mediators in dengue virus infection in children: interleukin-8 and its relationship to neutrophil degranulation. Infect Immun 2000;68(2):702-707.
Promphan W, Sopontammarak S, Pruekprasert P, Kajornwattanakul W, Kongpattanayothin A. Dengue myocarditis. Southeast Asian J Trop Med Public Health 2004;35(3):611-613.
Salgado D, Panqueba C, Vega R, Garzón M, Castro D, Rodríguez, J. Mortalidad por dengue hemorrágico en niños en Colombia: más allá del choque. Infectio 2008;12(1):247-253.
Salgado DM, Panqueba CA, Castro D, M RV, Rodriguez JA. Myocarditis in children affected by dengue hemorrhagic fever in a teaching hospital in Colombia. Rev Salud Pública (Bogotá). 2009;11(4):591-600.
Salgado DM, Eltit JM, Mansfield K, Panqueba C, Castro D, Vega MR, et al. Heart and Skeletal Muscle Are Targets of Dengue Virus Infection. Pediatr Infect Dis J 2010 Dec 21.
Green S, Rothman A. Immunopathological mechanisms in dengue and dengue hemorrhagic fever. Curr Opin Infect Dis 2006;19(5):429-436.
Avirutnan P, Malasit P, Seliger B, Bhakdi S, Husmann M. Dengue virus infection of human endothelial cells leads to chemokine production, complement activation, and apoptosis. J Immunol 1998 Dec. 1;161(11):6338-6646.
Warke RV, Xhaja K, Martin KJ, Fournier MF, Shaw SK, Brizuela N, et al. Dengue virus induces novel changes in gene expression of human umbilical vein endothelial cells. J Virol 2003;77(21):11822-11832.
Dengue hemorrhagic fever with special emphasis on immunopathogenesis. Comp Immunol Microbiol Infect Dis 2007;30(5-6):329-340.
Marianneau P, Steffan AM, Royer C, Drouet MT, Jaeck D, Kirn A, et al. Infection of primary cultures of human Kupffer cells by Dengue virus: no viral progeny synthesis, but cytokine production is evident. J Virol 1999;73(6):5201-5206.
King CA, Anderson R, Marshall JS. Dengue virus selectively induces human mast cell chemokine production. J Virol 2002;76(16):8408-8419.
King CA, Marshall JS, Alshurafa H, Anderson R. Release of vasoactive cytokines by antibodyenhanced dengue virus infection of a human mast cell/basophil line. J Virol 2000;74(15):7146-7150.
Nguyen TH, Lei HY, Nguyen TL, Lin YS, Huang KJ, Le BL, et al. Dengue hemorrhagic fever in infants: a study of clinical and cytokine profiles. J Infect Dis 2004;189(2):221-232.
Chaturvedi UC. Shift to Th2 cytokine response in dengue haemorrhagic fever. Indian J Med Res 2009;129(1):1-3.
Chaturvedi UC, Elbishbishi EA, Agarwal R, Raghupathy R, Nagar R, Tandon R, et al. Sequential production of cytokines by dengue virus-infected human peripheral blood leukocyte cultures. J Med Virol 1999;59(3):335-340.
Kurane I, Innis BL, Nimmannitya S, Nisalak A, Meager A, Janus J, et al. Activation of T lymphocytes in dengue virus infections. High levels of soluble interleukin 2 receptor, soluble CD4, soluble CD8, interleukin 2, and interferongamma in sera of children with dengue. J Clin Invest 1991;88(5):1473-1480.
Azeredo EL, Zagne SM, Santiago MA, Gouvea AS, Santana AA, Neves-Souza PC, et al. Characterisation of lymphocyte response and cytokine patterns in patients with dengue fever. Immunobiology 2001;204(4):494-507.
Kubelka CF, Borges PA, VonSydow FF, Lampe E. Analysis of tumor necrosis factoralpha serum level in Brazilian patients with Dengue-2. Mem Inst Oswaldo Cruz 1995;90(6):741-742.
Atrasheuskaya A, Petzelbauer P, Fredeking TM, Ignatyev G. Anti-TNF antibody treatment reduces mortality in experimental dengue virus infection. FEMS Immunol Med Microbiol 2003;35(1):33-42.
Huang YH, Lei HY, Liu HS, Lin YS, Liu CC, Yeh TM. Dengue virus infects human endothelial cells and induces IL-6 and IL-8 production. Am J Trop Med Hyg 2000;63(1-2):71-75.
Bozza FA, Cruz OG, Zagne SM, Azeredo EL, Nogueira RM, Assis EF, et al. Multiplex cytokine profile from dengue patients: MIP-1beta and IFN-gamma as predictive factors for severity. BMC Infect Dis 2008;8:86.
Srikiatkhachorn A, Green S. Markers of Dengue Disease Severity. Current Topics in Microbiology and Immunology 2009;1(2):68-79.
Zivna I, Green S, Vaughn DW, Kalayanarooj S, Stephens HA, Chandanayingyong D, et al. T cell responses to an HLA-B*07-restricted epitope on the dengue NS3 protein correlate with disease severity. J Immunol 2002;168(11):5959-5965.
Restrepo BN, Ramírez R, Arboleda M, Álvarez G, Ospina M, Díaz FJ. Levels of cytokines in two ethnic groups with dengue virus infection. Am J Trop Med Hyg 2008;79(5):673-677.