Despite the fact that our study could identify cytokines with good accuracy for the stratification and/or prognosis of dengue, it has potential limitations. Here we identified cytokines related to dengue severity, but the small sample size represents a shortcoming regarding the generalization of our results. In addition, only one time point was used for the measurement of cytokines, not allowing further insights provided by sequential measurements. Moreover, classification of disease severity has been a matter of debate, especially for adult patients' management and classification. Indeed, the WHO criteria for DHF has failed to identify severe disease, including fatal cases, in adult Latin America population [24, 54] (S.M.O. Zagne, R.M.O. Nogueira, unpublished) and clearly do not satisfy the stratification of our studied population. Accordingly, in the present study severe disease forms were classified following other proposed criteria [24] . While a direct correlation of cytokine concentrations and the pathophysiology of severe dengue is tempting, we believe that the full burden of disease severity cannot be attributed to a single cytokine. Cytokines may be increased simply as one of the several steps in the network loops without necessarily playing a direct harmful role and most likely more than one factor may be involved, including others not tested here such as IL-18, TGF-β, and MIF among others [9] .