Role of interleukin-12 in patients with dengue hemorrhagic fever

Abstract

Interleukin (IL)-12 has a broad range of activities including regulation of cytokine synthesis and selective promotion of Th1-type cell development. A shift from a Th1-type response to Th2-type has been suggested to be important in the pathogenesis of dengue hemorrhagic fever (DHF). This study was undertaken to investigate the possible role of IL-12 in this shift. A total of 76 patients with various grades of dengue illness and 21 normal healthy controls were tested for IL-12 levels in serum samples and IL-12 mRNA in their peripheral blood mononuclear cells. The results showed that the levels of IL-12 were the highest in patients with dengue fever (270+/-102 pg ml(-1)) followed by decreasing levels in the patients with DHF grade I (198+/-86 pg ml(-1); P<0.05) and DHF grade II (84+/-52 pg ml(-1); P<0.001). Neither IL-12 nor its mRNA could be detected in the patients with DHF grades III and IV. The cytokine appeared and reached peak levels during the first 4 days of illness, started to decline by day 5-8 and disappeared by day 9 onwards. The absence of IL-12 during severe illness and late phases of the disease may be responsible for the shift to a Th2-type response and thus for the pathogenesis of DHF.

The Cytokine Response of U937-Derived Macrophages Infected through Antibody-Dependent Enhancement of Dengue Virus Disrupts Cell Apical-Junction Complexes and Increases Vascular Permeability

“…The "cytokine storm" described years ago as the excessive release of proinflammatory cytokines in several infectious diseases has been associated to SD (38). This phenomenon is supported by several clinical and in vitro studies in which increased concentrations of TNF-␣, IL-6, IL-1␤, IL-8, IL-12p70, IL-10, and PGE2 were connected to hemorrhage and to the immune response observed in human peripheral blood mononuclear cells (PBMCs) obtained from patients with SD (39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49). Our data suggest a cytokine secretion profiles that is more specific than a "storm" in macrophages infected under ADE conditions that may play a leading role in the pathogenesis of VPS by inducing a bias toward a T-helper-2 response (50).…”

Immunopathogenesis of Dengue Hemorrhagic Fever

“…The levels of IL-12 are higher in DF than DHF patients. No IL-12 could be detected in patients with DHF grades III and IV [22] . This deficiency in IL-12 production might lead to a shift to the Th2-type response and inappropriate CTL generation.…”

Interleukin-18 levels in adult dengue fever and dengue hemorrhagic fever

“…7 Unlike IL-12 which was high in DF and absent in patients with DHF especially grade III and IV; all of the Th 2 type cytokines are high in DHF/severe dengue infection. [8][9][10] A recent study has shown that IL-18 is a potent co inducer of IL-13 in NK cells and Th cells (Th 2 ). It can act as a strong co inducer of Th 1 or Th 2 cytokines.…”