High levels of interferon alpha in the sera of children with dengue virus infection

Department of Medicine, University of Massachusetts Medical Center, Worcester.
The American journal of tropical medicine and hygiene (Impact Factor: 2.74). 02/1993; 48(2):222-9.
Source: PubMed

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.

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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) [2] [3]. Cases of dengue are characterized by an uncontrolled inflammatory response [2] [4], 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 [5] [6] [7] [8] [9] [10]. Monocytes are considered as the main target of DENV [11] 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. "
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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). "
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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. "
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