Cytokine cascade in dengue hemorrhagic fever: implications for pathogenesis

Chaturvedi, U. C.; Agarwal, Rajeev; Elbishbishi, E.A.; Mustafa, Abu Salim

doi:10.1111/j.1574-695x.2000.tb01474.x

Cited by 240 publications

(71 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The implication of IgE in increased vascular permeability has been reported in the past [34]. Proinflammatory cytokines, such as IL-1b and tumor necrosis factor-a, triggered by IgE-containing immune complexes may contribute to this phenomenon [35,36]. A shift from Th1 to Th2 responses during dengue virus infection might lead to elevated IgE antibodies in serum [37].…”

Section: Discussionmentioning

confidence: 98%

Higher levels of dengue-virus-specific IgG and IgA during pre-defervescence associated with primary dengue hemorrhagic fever

et al. 2015

View full text Add to dashboard Cite

Dengue hemorrhagic fever (DHF), although predominantly associated with secondary infections, has also been reported in primary infections. An enhanced immune response including antibodies and cytokines is implicated in the pathogenesis of secondary DHF. However, the factors operating in primary DHF are poorly understood. To understand the role of the antibody response, the relative levels of different antibody isotypes during the acute phase of infection in primary and secondary dengue infections were determined. Levels of DENV-specific IgM, IgG, IgA and IgE were measured in the serum samples of 200 dengue patients and 20 dengue-naïve individuals. Samples were collected within 15 days of onset of illness. The DENV-specific IgM levels were significantly higher in DF cases compared to DHF, which was more evident in secondary infections and in post-defervescence samples. The levels of IgG, IgA and IgE were higher in DHF cases, with greater significance in primary infections. A higher level of IgG in DHF cases was evident in pre-defervescence samples, whilst the IgE level was higher in pre- and post-defervescence samples. There was a significant correlation of IgG titres with platelet counts, with higher titres associated with lower platelet counts. It is speculated that IgG, IgA and IgE produced in response to primary infections may contribute to pathogenesis, whilst IgM produced in response to secondary infections may protect against progression to severe disease.

show abstract

Section: Discussionmentioning

confidence: 98%

Higher levels of dengue-virus-specific IgG and IgA during pre-defervescence associated with primary dengue hemorrhagic fever

et al. 2015

View full text Add to dashboard Cite

show abstract

“…These complications usually occur during or shortly after defervescence in the so-called critical phase. The precise pathogenesis of these complications is not yet fully understood, but a massive secretion of cytokines by activated monocytes/macrophages and T lymphocytes is assumed to play a pivotal role (3)(4)(5)(6).…”

mentioning

confidence: 99%

Normal Free Interleukin-18 (IL-18) Plasma Levels in Dengue Virus Infection and the Need To Measure Both Total IL-18 and IL-18 Binding Protein Levels

Michels

Mast

Netea

et al. 2015

Clin Vaccine Immunol

View full text Add to dashboard Cite

bActivated monocytes/macrophages and T lymphocytes that produce a cytokine storm are assumed to play a pivotal role in the pathogenesis of dengue. Interleukin-18 (IL-18) is a proinflammatory cytokine that is increased during dengue and known to induce gamma interferon (IFN-␥), which is crucial for dengue immune response. No data are available regarding the balance between IL-18 and its natural inhibitor IL-18 binding protein (IL-18BP) and how they interact within the inflammatory reaction of patients with dengue virus infections. Circulating levels of IL-18; IL-18BP; free, biologically active IL-18; the IL-18-dependent proinflammatory cytokine IFN-␥; monocyte-derived cytokines; and ferritin were assessed in adult Indonesian dengue patients (n ‫؍‬ 95). Healthy individuals (n ‫؍‬ 22) and leptospirosis (n ‫؍‬ 19) and enteric fever (n ‫؍‬ 6) patients served as controls. Total IL-18 levels were increased during dengue, leptospirosis, and enteric fever compared to healthy controls. However, due to a concurrent increase in IL-18BP levels, biologically active IL-18 levels remained similar in the different phases of dengue and in patients with leptospirosis. Biologically active IL-18 levels were also similar in patients with severe and nonsevere dengue. In conclusion, high total IL-18 and IL-18BP levels concur in dengue virus infections, leptospirosis, and enteric fever. This resulted in unchanged levels of free, biologically active IL-18 in dengue and leptospirosis, which underlines the importance of measuring both IL-18 and IL-18BP when studying the role of IL-18 in diseases. Dengue has become one of the most important arboviral infections in the world (1). Dengue virus infection usually manifests as a self-limiting febrile illness. A subset of patients, however, develops life-threatening complications, which include plasma leakage, bleeding, and/or severe organ failure (2, 3). These complications usually occur during or shortly after defervescence in the so-called critical phase. The precise pathogenesis of these complications is not yet fully understood, but a massive secretion of cytokines by activated monocytes/macrophages and T lymphocytes is assumed to play a pivotal role (3-6).Interleukin-18 (IL-18) is a member of the IL-1 family of cytokines. It is synthesized as an inactive precursor requiring processing by caspase-1 into an active cytokine. The precursor is constitutively expressed by nearly all cells in humans. Dengue virus has been shown to activate the inflammasome and induce the production of IL-18 by human macrophages (7). IL-18, together with IL-12, plays a major role in the production of gamma interferon (IFN-␥). This was also shown in a murine dengue model, in which IL-18 acted in synergism with IL-12 to induce IFN-␥ and other T-helper 1 cytokines, which are considered central mediators in dengue host defense (8, 9).Previous studies in patients with acute dengue have reported high serum IL-18 levels, which correlated with disease severity (10-12). However, the activity of IL-18 is balanced by a natura...

show abstract

“…There is increasing evidence that the immune system plays a key role in determining the severity of dengue disease [18,19], in particular the array of cytokines produced during infection [8,9,10,24]. The role of T lymphocytes in this process is controversial since on the one hand there is evidence that activation of T lymphocytes leads to pro-inflammatory cytokine synthesis [20,21,22,23,24,25,26,27] and on the other there is evidence that T-lymphocyte proliferation in dengue patients is impaired [28,29,30,31] and that patients with acute DENV infection are leukopenic [28,29].…”

Section: Discussionmentioning

confidence: 99%

“…The mechanisms that lead to these clinical outcomes are unknown, however there is growing evidence that the pathophysiology of dengue is mediated by host immune response [2,4]. Several lines of evidence indicate that anti-dengue antibodies [5,6,7], cytokines [8,9,10], soluble immune mediators [11,12,13] and cross-reactive memory T lymphocytes [14,15,16], along with high dengue viral loads [17], contribute to the progression to DHF/DSS and death [18,19]. …”

Section: Introductionmentioning

confidence: 99%

Dengue Virus Serotype-2 Impairs Proliferation of Healthy Donors' T Lymphocytes

et al. 2014

View full text Add to dashboard Cite

Objectives: T lymphocytes are not infected by dengue virus (DENV), nevertheless it is possible that exposure to DENV may affect their function. T lymphocytes from DENV-infected individuals are impaired in their proliferative capacity, although this effect has been attributed to altered function of antigen-presenting cells rather than to an intrinsic defect on T lymphocytes. Here we analyzed whether T lymphocytes from healthy donors became impaired in their proliferative capacity following in vitro exposure to DENV serotype-2 (DENV-2), as well as the possible mechanisms for this. Methods: Isolated CD4+ and CD8+ T lymphocytes from healthy donors were in vitro exposed to DENV-2, before polyclonal activation, cell proliferation, IL-2 synthesis. IL-2Rα expression, nuclear translocation of NF-AT and NF-κB, and intracellular calcium flux were assessed. Results: In vitro exposure of both CD4+ and CD8+ T lymphocytes from healthy donors to DENV-2 impairs cell proliferation, IL-2 synthesis, and IL-2Rα (CD25) cell membrane expression. Signalling wise, exposure to DENV-2 impairs the nuclear translocation of NF-AT, downstream of intracellular calcium mobilization, as well as that of NF-κB. Conclusion: In the course of a dengue infection, direct exposure of T lymphocytes to DENV could affect cell-mediated immune responses.

show abstract

Cytokine cascade in dengue hemorrhagic fever: implications for pathogenesis

Cited by 240 publications

References 30 publications

Higher levels of dengue-virus-specific IgG and IgA during pre-defervescence associated with primary dengue hemorrhagic fever

Higher levels of dengue-virus-specific IgG and IgA during pre-defervescence associated with primary dengue hemorrhagic fever

Normal Free Interleukin-18 (IL-18) Plasma Levels in Dengue Virus Infection and the Need To Measure Both Total IL-18 and IL-18 Binding Protein Levels

Dengue Virus Serotype-2 Impairs Proliferation of Healthy Donors' T Lymphocytes

Contact Info

Product

Resources

About