Levels of soluble ST2 in serum associated with severity of dengue due to tumour necrosis factor alpha stimulation

• Published in: Journal of general virology 2010-03, Vol.91 (3), p.697-706
• Main Authors: Houghton-Trivino, Natalia, Salgado, Doris M, Rodriguez, Jairo A, Bosch, Irene, Castellanos, Jaime E
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Biological and medical sciences; Biomarkers; Cell Line; Cells, Cultured; Child; Child, Preschool; Dengue - diagnosis; Dengue - immunology; Dengue - pathology; Endothelial Cells - immunology; Enzyme-Linked Immunosorbent Assay - methods; Female; Fundamental and applied biological sciences. Psychology; Gene Expression Profiling; Humans; Interleukin-1 Receptor-Like 1 Protein; Leukocytes, Mononuclear - immunology; Male; Microbiology; Middle Aged; Miscellaneous; Receptors, Cell Surface - blood; Reverse Transcriptase Polymerase Chain Reaction - methods; Serum - chemistry; Tumor Necrosis Factor-alpha - immunology; Virology; Young Adult
• ISSN: 0022-1317; 1465-2099
• DOI: 10.1099/vir.0.012971-0

1 Grupo de Virología, Universidad El Bosque, Carrera 7B Bis No. 132-11, Bogota, Colombia 2 Grupo Parasitología y Medicina Tropical, Universidad Surcolombiana, Neiva, Colombia 3 Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, MA, USA 4 Grupo Patogénesis Viral, Universidad Nacional de Colombia, Bogota, Colombia Correspondence Jaime E. Castellanos castellanosjaime{at}unbosque.edu.co The interleukin-1 receptor-like-1 protein (IL1RL1), also known as ST2, has been shown previously to regulate T-cell function and is produced by T cells and endothelial cells. It was reported recently 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 haemorrhagic fever (DHF) and mild dengue fever (DF) were evaluated using a secreted soluble ST2 (sST2) ELISA. The RNA expression of ST2 was evaluated by real-time quantitative RT-PCR using patients' peripheral blood mononuclear cells (PBMCs) 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- ), interleukin (IL)-8 and IL-10 compared with DF patients and normal healthy control individuals. However, viraemia was indistinguishable between mild and severe cases. No changes in ST2 mRNA expression were found in PBMCs from these two groups of dengue patients. In vitro , sST2 was elevated in HUVECs treated with patient sera. Neutralization of TNF- in patient sera by pre-treatment with a TNF- antibody inhibited the upregulation of sST2 expression in HUVECs. These results implicate serum TNF- in the modulation of expression of sST2 in an in vitro system, and indicate that sST2 could be associated with the severity of disease. Further studies to determine whether sST2 levels are predictive of the severe form of the disease and the role of sST2 in immune regulation are warranted. Present address: Centro de Investigaciones Biomédicas, Universidad Simón Bolívar, Barranquilla, Colombia.