High levels of interferon alpha in the sera of children with dengue virus infection
ABSTRACT We measured the levels of interferon alpha (IFN alpha) in the sera of Thai children hospitalized with dengue hemorrhagic fever (DHF) or dengue fever (DF) to examine the role of IFN alpha in dengue virus infections of humans. The percentage of patients who had detectable levels of IFN alpha (> or = 3 U/ml) was higher in patients with DHF (80%, P < 0.001) and in patients with DF (60%, P < 0.001) than in healthy Thai children (7%). The levels of IFN alpha were higher in patients with DHF and in patients with DF on the first few days after the onset of fever than in healthy Thai children. The average levels of IFN alpha in patients with DHF were high two days before defervescence, decreasing gradually until the day of defervescence. There was a subset of patients with DHF who had increasing levels of IFN alpha after defervescence. However, the levels of IFN alpha in patients with DF were not high after fever subsided. The levels of IFN alpha were not different among children with DHF grades 1, 2 and 3. Among patients with DHF, T lymphocytes were activated to a higher degree in high IFN alpha producers than in low IFN alpha producers. These results indicate that similarly high levels of IFN alpha are produced in vivo during the acute stages of DHF and DF, and that high levels of IFN alpha remain after fever subsides in some patients with DHF, but not in patients with DF.
- SourceAvailable from: Hector Vivanco-Cid
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- "Infection with any of the DENV serotypes (DENV-1, -2, -3, and -4) is generally asymptomatic, but many cases develop dengue fever (DF) or result in severe forms of the disease, known as dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS)  . Cases of dengue are characterized by an uncontrolled inflammatory response  , with massive production of soluble factors such as TNF-<alpha>, IFN-<alpha>, IL-6, IL-8, IL-10 and HMGB1, which are related to disease severity      . Monocytes are considered as the main target of DENV  and recently, Wong et al. demonstrated that different subpopulations of these cells (CD16 + and CD16 − ) are permissive to infection and capable of support the production of new infective virus particles. "
ABSTRACT: Uncontrolled and intricate production of inflammatory factors is the characteristic feature of dengue infection. The triggering receptor expressed in myeloid cells-1 (TREM-1), expressed on the surface of monocytes and neutrophils, is capable of enhancing and regulating the inflammatory response via the production of different mediators in bacterial and viral infections. Here, both the expression of TREM-1 on human monocytes and neutrophils from peripheral blood of dengue infected individuals, as well as the levels of the soluble form of TREM-1 (sTREM-1) in the sera of these patients were compared against healthy controls. A significant reduction of TREM-1 expression was observed in neutrophils during the first days of infection, followed by a gradual recovery throughout the course of infection. Also, sera from DENV-infected patients exhibited significantly higher sTREM-1 levels than healthy individuals. The difference was more pronounced during the first 5 days after the onset of symptoms. These findings highlight the dynamic process of TREM-1 expression during DENV infection. We hypothesized that increment of free sTREM-1 could be a compensatory mechanism aiming to counteract the inflammatory process elicited during DENV infection.Immunology letters 01/2014; 158(1-2). DOI:10.1016/j.imlet.2014.01.003 · 2.37 Impact Factor
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- "Proinflammatory cytokines, such as TNF-α, IFN-γ, IL-6, IL-18 and macrophage migration inhibitory factor (MIF), are also known to be involved during the acute phase of the illness (Pinto et al. 1999, Braga et al. 2001, Bozza et al. 2008, Levy et al. 2010) and many chemokines involved in leukocyte recruitment to sites of infection, such as CXCL8/IL-8, CXCL10/inducible protein-10 (IP-10) and CCL2/monocyte chemotactic protein-1 (MCP-1), are produced during inflammation (Raghupathy et al. 1998, Hsieh et al. 2006, Lee et al. 2006). One study showed elevated IFN-α plasma levels shortly after symptom onset in DF children (Kurane et al. 1993). The severity of DENV infection seems to be due more to disproportionate inflammatory cytokine production than direct viral effects (Chaturvedi et al. 2007, Rothman 2009). "
ABSTRACT: Dengue virus (DENV) and parvovirus B19 (B19V) infections are acute exanthematic febrile illnesses that are not easily differentiated on clinical grounds and affect the paediatric population. Patients with these acute exanthematic diseases were studied. Fever was more frequent in DENV than in B19V-infected patients. Arthritis/arthralgias with DENV infection were shown to be significantly more frequent in adults than in children. The circulating levels of interleukin (IL)-1 receptor antagonist (Ra), CXCL10/inducible protein-10 (IP-10), CCL4/macrophage inflammatory protein-1 beta and CCL2/monocyte chemotactic protein-1 (MCP-1) were determined by multiplex immunoassay in serum samples obtained from B19V (37) and DENV-infected (36) patients and from healthy individuals (7). Forward stepwise logistic regression analysis revealed that circulating CXCL10/IP-10 tends to be associated with DENV infection and that IL-1Ra was significantly associated with DENV infection. Similar analysis showed that circulating CCL2/MCP-1 tends to be associated with B19V infection. In dengue fever, increased circulating IL-1Ra may exert antipyretic actions in an effort to counteract the already increased concentrations of IL-1β, while CXCL10/IP-10 was confirmed as a strong pro-inflammatory marker. Recruitment of monocytes/macrophages and upregulation of the humoral immune response by CCL2/MCP-1 by B19V may be involved in the persistence of the infection. Children with B19V or DENV infections had levels of these cytokines similar to those of adult patients.Memórias do Instituto Oswaldo Cruz 02/2012; 107(1):48-56. DOI:10.1590/S0074-02762012000100007 · 1.57 Impact Factor
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- "Alternatively, some intrinsic factors may regulate virus production per cell. Among intrinsic factors, antiviral type I IFNs, IFNα/β, are elicited in patients with dengue fever, in DENV-infected human mononuclear cells in vitro, as well as in volunteers who have received candidate dengue vaccines in vivo (Chaturvedi et al., 1999; Green et al., 1999c; Kurane et al., 1993; Libraty et al., 2002; Sanchez et al., 2006; Ubol et al., 2008). If IFNα/β responses were suppressed and/or delayed during ADE infection, dengue viral replication might increase. "
ABSTRACT: It remains unclear whether antibody-dependent-enhancement (ADE) of dengue infection merely augments viral attachment and entry through Fcγ receptors or immune complex binding to Fcγ receptors triggers an intrinsic signaling cascade that changes the viral permissiveness of the cell. Using human dengue-immune sera and novel human monoclonal antibodies against dengue in combination with virologic and immunologic techniques, we found that ADE infection increased the proportion of infected primary human monocytes modestly from 0.2% ± 0.1% (no Ab) to 1.7% ± 1.6% (with Ab) but the total virus output markedly from 2 ± 2 (× 10(3)) FFU to 120 ± 153 (× 10(3))FFU. However, this increased virus production was not associated with a reduced secretion of type I interferon or an elevated secretion of anti-inflammatory cytokine, IL-10. These results demonstrate that the regulation of virus production in ADE infection of primary human monocytes is more complex than previously appreciated.Virology 02/2011; 410(1):240-7. DOI:10.1016/j.virol.2010.11.007 · 3.28 Impact Factor