Attached
O bjective: Platelet Activating Factor (PAF), was shown to be an important mediator of vascular
leak in acute dengue. Therefore, w e set out to investigate the factors that lead to PAF production
and its association with other severity markers in acute dengue. M ethods: PAF production by
primary human monocytes was assessed by co-culturing dengue virus (D E N V ) infected monocytes
with lipopolysaccharide (LPS) levels reported in patients with acute dengue, or dengue immune
sera at varying concentrations. G ene expression analysis was done for M APK1, MAPK3, M APK14,
NLRP-3, TLR-4, NF-KB, RIG-I.
Results: PAF was only produced by D EN V infected monocytes in the presence of LPS and was not
induced by the infection alone or in the presence of dengue immune sera. However, IL-6, IL-10 and
TN Fa were induced in D E N V infected monocytes in the absence of LPS and also in the presence
of dengue immune sera. PAF, IL-6, IL-10 and TN Fa levels were significantly higher in D E N V
infected monocytes co-cultured with LPS, than monocytes co-cultured with LPS alone. Although
the NFKp-1 pathway is known to be involved in inducing proinflammatory cytokines and PAF, only
RIG-I was significantly up regulated (p< 0.05) when D EN V infected monocytes were co-cultured
with LPS. M APK1, MAPK3, MAPK14, NLRP3 or TLR-4 m RNA not induced by D E N V infection of
monocytes or by co-cuituring D E N V infected monocytes with LPS.
C onclusion: Although LPS appears to act synergistically with the D E N V to induce PAF and other
cytokine production, the mechanisms by which this occurs needs further investigation.
