In a dengue intracerebral mouse infection models, CXCR3 2/2 and IP10 2/2 mice both had higher mortality rate than wild type mice after infection, indicating that IP-10 and CXCR3 receptors are part of the host defense mechanism, most likely in recruitment of T cells to the infection site [38] . IP-10 was also proposed to compete with virus binding on the receptor in vitro [39] . However, the relevance of this study to human patients is not clear. Although IFNc, a/b and NF-kB could all induce the production of IP-10 and I-TAC, prevention of IP-10 and I-TAC via NF-kB inhibition clearly reduced the IP-10 level in HepG2 cells. Furthermore, IFNb and IFNc were not consistently upregulated in the two cell lines or in DF patients in our study (data not shown). Therefore, we believe that NF-kB activation rather than IFN induction played the major role in elevated IP-10 and I-TAC in dengue infection. The inhibition of NF-kB, and consequent IP-10 and I-TAC inhibition, had no demonstrable effect on dengue replication in cell lines, suggesting the more complex role for these chemokines in a multi-cellular in vivo setting. Concentrations of each chemokine were significantly higher during the early stages of dengue fever, while I-TAC levels were reduced at the second visit, IP-10 levels remained high. The persistently high level of IP-10 might also contribute to the immunopathogenesis of dengue although this would require further investigation. It may be that concentrations of IP-10 and I-TAC, in combination with a viral antigen, could be used as an early marker for dengue fever. It is interesting to note that the level of IP-10 and I-TAC were independent of previous history of dengue infection, as half of the ten tested patients were suffering from a secondary infection. The common clinical feature of the ten selected patients was the low platelet count at second visit. Because of the lack of severe dengue cases (by WHO definition) in Singapore, the low platelet count was used as the measure of severity by which the ten patients from the cohort study were classified as having more severe dengue fever. We cannot at this point make a link between the level of IP-10, I-TAC and disease severity because of the small number of cases used in this study, a more detailed clinical study, currently underway, aims to determine if the concentrations of IP-10 and I-TAC during early stages of infection are linked to the progression to more severe forms of disease.