Primary dengue virus infections induce differential cytokine production in Mexican patients|
Hernández, Sergio Isaac de la Cruz; Puerta-Guardo, Henry Nelson; Aguilar, Hilario Flores; Mateos, Silvia González; Martinez, Irma López; Ortiz-Navarrete, Vianney; Ludert, Juan E. & Angel, Rosa María del
Severe dengue pathogenesis is not fully understood, but high levels of proinflammatory cytokines have been associated
with dengue disease severity. In this study, the cytokine levels in 171 sera from Mexican patients with primary dengue
fever (DF) and dengue haemorrhagic fever (DHF) from dengue virus (DENV) 1 (n = 116) or 2 (n = 55) were compared.
DF and DHF were defined according to the patient’s clinical condition, the primary infections as indicated by
IgG enzymatic immunoassay negative results, and the infecting serotype as assessed by real-time reverse transcriptionpolymerase
chain reaction. Samples were analysed for circulating levels of interleukin (IL)-12p70, interferon (IFN)-γ,
tumour necrosis factor (TNF)-α, IL-6, and IL-8 using a commercial cytometric bead array. Significantly higher IFN-γ
levels were found in patients with DHF than those with DF. However, significantly higher IL-12p70, TNF-α, and IL-6
levels were associated with DHF only in patients who were infected with DENV2 but not with DENV1. Moreover, patients
with DF who were infected with DENV1 showed higher levels of IL-12p70, TNF-α, and IL-6 than patients with
DHF early after-fever onset. The IL-8 levels were similar in all cases regardless of the clinical condition or infection
serotype. These results suggest that the association between high proinflammatory cytokine levels and dengue disease
severity does not always stand, and it once again highlights the complex nature of DHF pathogenesis.
dengue haemorrhagic fever; dengue pathogenesis; cytokines