TNF and infection: TNF has previously been identified to promote the severe vascular leakage that occurs in DENV-infected animals (Atrasheuskaya et al., 2003) and our data that leukotrienes and proteases also promote vascular leakage during infection with DENV suggests that multiple mediators, a substantial portion of them MC-derived, likely act in concert to effectuate the vascular complications that occasionally occur during severe DENV infections (Figure 7).