Platelet activating factor and its association with other inflammatory mediators in the pathogenesis of dengue

Abstract

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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.