Ánalisis de la respuesta inmunitaria inflamatoria en la inflamación por el virus dengue y su significancia clínica

Resumo

Dengue is a viral disease, of endemic-epidemic character, is the most important arbovirus diseases worldwide in terms of morbidity, mortality and economic impact. Cytokines and apoptosis play an important role in the immune response against dengue virus (DENV), yet its presence in the severe form of the disease is not completely understood. The aim of this study was to evaluate the cytokine pattern proinflammatory/anti-inflammatory and TRAIL apoptosis marker in patients with dengue and its clinical significance, with emphasis on developmental stages, severity, viral serotype and type of infection. In addition, we examined the effect of DENV on cytokine production in cultured PBMC and apoptosis in monocytes from patients with dengue and infected at different days with the dengue virus. In this regard, we determined the concentration of pro-inflammatory cytokines (tumor necrosis factor-α [TNF], interleukin 6 [IL-6], IL-1β, IL-12 and IL-17, anti-inflammatory (receptor 1 soluble TNF [sTNF-RI], sTNF-RII, and protein 1 type receptor of interleukin-1 [IL1RL1/sST2]) and the apoptosis marker related apoptosis-inducing ligand and tumor necrosis factor [sTRAIL] in thirty patients with dengue in the acute phase, early recovery phase and late recovery phase. These patients were classified according to the severity of the disease by the WHO criteria for dengue no warning signs, dengue warning signs and severe dengue and the type of infection in primary infection (PI) and secondary infection (SI). We included two control groups, ten healthy subjects (control) and eight with other febrile viral infection (OIVF). Circulating levels of cytokines were determined by ELISA and apoptosis by TUNEL method. PBMC cultures were stimulated or not with LPS for 24 hours. Our results showed a significant increase in most of the cytokines pro-and anti-inflammatory (TNF, IL-6, IL-12, IL-17, sTNF-RI, sTNF-RII, IL1RL1/sST2) and sTRAIL in serum of patients with dengue in the acute phase of the disease respect to the control group. Increased IL-6, sTNF-RI, sTNF-RII and IL1RL1/sST2 was associated with the severity of the disease, while IL-12 did not change during severe illness. The increase of sTRAIL was evident in the primary infection. The pattern of secretion of cytokines TNF and IL-1β in infected monocytes was similar when comparing the concentrations with the control group without stimulation. Furthermore, levels of IL-6 and IL-12 similar to the control group were enrolled. Monocytes from patients with dengue without LPS showed increased apoptotic cells (p<0.001) compared to the control. This increase in cytokine and apoptosis during the illness evidence participation of DENV in the activation and death of monocyte in vivo.