The manipulation or intervention of TLR-mediated immune responses is a potential approach to treat and prevent the septic shock and variety of associated diseases. However, blocking TLR may lead to 'inappropriate' immune responses such allergic Th2 responses, or immunological tolerance (78) . Thus, it seems clear that the risks and benefits of manipulation of TLR mediated immune responses need to be balanced and require further investigation. Multiplex cytokine profile from dengue patients: MIP-1beta and IFN-gamma as predictive factors for severity BACKGROUND: Dengue virus pathogenesis is not yet fully understood and the identification of patients at high risk for developing severe disease forms is still a great challenge in dengue patient care. During the present study, we evaluated prospectively the potential of cytokines present in plasma from patients with dengue in stratifying disease severity. METHODS: Seventeen-cytokine multiplex fluorescent microbead immunoassay was used for the simultaneous detection in 59 dengue patients. GLM models using bimodal or Gaussian family were determined in order to associate cytokines with clinical manifestations and laboratory diagnosis. RESULTS: IL-1β, IFN-γ, IL-4, IL-6, IL-13, IL-7 and GM-CSF were significantly increased in patients with severe clinical manifestations (severe dengue) when compared to mild disease forms (mild dengue). In contrast, increased MIP-1β levels were observed in patients with mild dengue. MIP-1β was also associated with CD56+NK cell circulating rates. IL-1β, IL-8, TNF-α and MCP-1 were associated with marked thrombocytopenia. Increased MCP-1 and GM-CSF levels correlated with hypotension. Moreover, MIP-1β and IFN-γ were independently associated with both dengue severity and disease outcome. CONCLUSION: Our data demonstrated that the use of a multiple cytokine assay platform was suitable for identifying distinct cytokine profiles associated with the dengue clinical manifestations and severity. MIP-β is indicated for the first time as a good prognostic marker in contrast to IFN-γ that was associated with disease severity. During the last decades dengue became the most important arthropod-borne emerging viral disease in tropical countries [1] . It is estimated that about 2.5% notified cases are classified as dengue haemorrhagic fever (DHF) and about 2.5-20% of DHF cases are lethal [2] [3] [4] . In the last two decades, Latin America saw a dramatic increase in frequency and in geographic extension of dengue fever. Specifically, the situation in Brazil has worsened during the last decade since the introduction of the Dengue-3 serotype. In the past years Brazil had dengue outbreaks with at least 1 million cases (2001) (2002) and within the last 18 months 900 thousand cases were reported [5] . In addition, severe disease forms are occurring with increased frequency and mortality rates.