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Published online ahead of print on 4 November 2009 as doi:10.1099/vir.0.012971-0
J Gen Virol (2009), DOI 10.1099/vir.0.012971-0
© 2009 Society for General Microbiology

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Levels of soluble ST2 in serum associate with severity of dengue due to TNF-{alpha} stimulation

Natalia Houghton-Triviño1, Doris M Salgado2, Jairo A Rodriguez2, Irene Bosch3 and Jaime E Castellanos1,4

1 Grupo de Virologia, Universidad El Bosque, Bogota, Colombia;
2 Grupo de Parasitologia y Medicina Tropical, U. Surcolombiana, Neiva, Colombia;
3 U. Massachussets Medical School

4 E-mail: castellanosjaime{at}unbosque.edu.co

The interleukin-1 receptor-like-1 protein (IL1RL-1), also known as ST2, has been previously shown to regulate T cell function and is produced by T cells and endothelial cells. It was recently reported to be elevated in mild dengue patients during acute disease. The ST2 gene encodes several splice products: L (long), V (short) and s (soluble). A cohort of 38 patients with dengue hemorrhagic fever (DHF) and mild dengue fever (DF) were evaluated using sST2 ELISA. The RNA expression of ST2 was evaluated by real time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) using patients’ peripheral mononucleated blood cells (PMBCs) and in vitro using human umbilical vein endothelial cells (HUVECs) exposed to sera from dengue patients. DHF patients had higher levels of serum sST2, tumour necrosis factor alpha (TNF-{alpha}, interleukin-8 and interleukin-10 compared to DF patients and normal healthy control individuals. However, viremia was indistinguishable between mild and severe cases. No changes in ST2 mRNA expression in PBMCs were found in these two groups of dengue patients. In vitro, sST2 was elevated in HUVECs treated with patients' sera. Neutralisation of TNF-{alpha} in patient sera by pre-treatment with a TNF antibody inhibited the up-regulation of sST2 expression in HUVECs. These results implicate serum TNF-{alpha} in the modulation of expression of sST2 in an in vitro system and sST2 could be associated with severity of disease. Further studies to determine if sST2 levels are predictive of the severe form of the disease as its role in immune regulation are warranted.

Received 23 April 2009; accepted 31 October 2009.





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