The Role of Cytokines in Activation of Coagulation and Fibrinolysis in Dengue Shock Syndrome

Suharti, Catharina; Gorp, Eric C. M. Van; Setiati, Tatty E.; Dolmans, W.M.V.; Djokomoeljanto, R.; Hack, C. E.; Cate, Hugo Ten; Meer, J.W.M. van der

doi:10.1055/s-0037-1612941

Cited by 101 publications

(88 citation statements)

References 23 publications

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“…DENV-2 has been the serotype most associated with disease severity in the course of a secondary infection, [33][34][35][36][37] and high levels of TNF-α and IFN-γ have been frequently associated with severe dengue. 6,28,[54][55][56][57][58][59][60] This finding is not consistent with higher IFNγ and TNF-α responses observed in PBMC from dengue-naive persons in response to DENV-2 challenge, especially if one considers that DENV-2 primary infection is frequently mild or asymptomatic. However, IFN-γ and TNF-α are essential for effective control of viral infection.…”

Section: Discussionmentioning

confidence: 69%

Variation in Inflammatory/Regulatory Cytokines in Secondary, Tertiary, and Quaternary Challenges with Dengue Virus

Sierra

Pérez²,

Álvarez³

et al. 2012

The American Society of Tropical Medicine and Hygiene

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Abstract. Secondary heterologous dengue infection is a risk factor for severe disease manifestations because of the immune-enhancement phenomenon. Succeeding clinical infections are seldom reported, and the clinical course of tertiary and quaternary dengue infections is not clear. Cuba represents a unique environment to study tertiary/quaternary dengue infections in a population with known clinical and serologic dengue markers and no dengue endemicity. We took advantage of this exceptional epidemiologic condition to study the effect of primary, secondary, tertiary, and quaternary dengue infection exposure on the expression of pro-inflammatory and regulatory cytokines, critical in dengue infection pathogenesis, by using a dengue infection ex vivo model. Whereas secondary exposure induced a high cytokine response, we found a significantly lower expression of tumor necrosis factor-α, interferon-γ, interleukin-10, and tumor growth factor-β after tertiary and quaternary infectious challenge. Significant differences in expression of the cytokines were seen between the dengue immune profiles, suggesting that the sequence in which the immune system encounters serotypes may be important in determining the nature of the immune response to subsequent infections.

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Section: Discussionmentioning

confidence: 69%

Variation in Inflammatory/Regulatory Cytokines in Secondary, Tertiary, and Quaternary Challenges with Dengue Virus

Sierra

Pérez²,

Álvarez³

et al. 2012

The American Society of Tropical Medicine and Hygiene

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“…into mice, we found it could increase Plm activity and D-dimer level in mouse PPP. Thus, DENV-induced Plg cross-reactive Abs may contribute to hyperfibrinolysis, as found in DENV-infected nonhuman primate and DHF/DSS patients (25)(26)(27). In addition, it is known that local fibrin clot formation may be implicated in host defense against microbial pathogens (28).…”

Section: Discussionmentioning

confidence: 98%

Dengue Virus-Induced Autoantibodies Bind to Plasminogen and Enhance Its Activation

Chuang

Lei

Lin

et al. 2011

The Journal of Immunology

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Dengue virus infection can lead to life-threatening dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS) in patients. Abnormal activation of the coagulation and fibrinolysis system is one of the hallmarks associated with DHF/DSS patients. However, the mechanisms that cause pathology in DHF/DSS patients are still unclear. Because conversion of plasminogen (Plg) to plasmin (Plm) is the first step in the activation of fibrinolysis, Abs against Plg found in DHF/DSS patients may be important. Therefore, to investigate the specificity, function, and possible origin of these Abs, we generated several Plg cross-reactive mAbs from DENV-immunized mice. An IgG mAb, 6H11, which recognizes an epitope associated with a dengue envelope protein, demonstrated a high level of cross-reactivity with Plg. The 6H11 Ab was further characterized with regard to its effect on Plg activation. Using Plm-specific chromogenic substrate S-2251, we found that mAb 6H11 demonstrated serine protease activity and could convert Plg directly to Plm. The serine protease activity of mAb 6H11 was further confirmed using serine protease chromogenic substrate S-2288. In addition, we found several Plg cross-reactive mAbs that could enhance urokinase-induced Plg activation. Lastly, mAb 6H11 could induce Plm activity and increase the level of D-dimer (a fibrin degradation product) in both human and mouse platelet-poor plasma. Taken together, these data suggest DENV-induced Plg cross-reactive Abs may enhance Plg conversion to Plm, which would be expected to contribute to hyperfibrinolysis in DHF/DSS patients.

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“…IL-6, for example, is thought to act over the extrinsic pathway of coagulation through tissue factor expression [17], whereas TNF-␣ is thought to play a direct role in the activation pathway of the fibrinolytic system [18,19]. Thus, the present study was aimed at analyzing the possible association between TNF-␣, IL-6 and D-dimer or TATc levels in patients with different stages of NSCLC, to better characterize the possible link between these inflammatory cytokines and fibrinolysis activation in NSCLC.…”

Section: Introductionmentioning

confidence: 99%

Correlation between tumor necrosis factor-alpha and d-dimer levels in non-small cell lung cancer patients

Guadagni¹,

Ferroni

Basili

et al. 2004

Lung Cancer

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KEYWORDSNon-small-cell lung cancer; Fibrinolysis; Coagulation;Tumor necrosis factor-alpha; D-Dimer; Thrombin-antithrombin complexes Summary The present study was designed to investigate whether a correlation exists between IL-6, TNF-␣ and coagulation (Thrombin-antithrombin, TATc) or fibrinolysis (D-dimer) activation in non-small cell lung cancer (NSCLC) patients. One hundred thirty patients with NSCLC (n = 65, 53 males, mean age 65 ± 8, adenocarcinoma n = 32, squamous cancer n = 33) or chronic obstructive pulmonary disease (COPD) (n = 65, 51 males, mean age 67 ± 9) were studied. As control group 65 healthy donors (51 males, mean age 61 ± 14) were also evaluated. The results obtained showed that median D-dimer levels were higher in NSCLC patients (3.0 g/ml) compared either to COPD patients (1.1 g/ml, P < 0.05) or controls (0.3 g/ml, P < 0.0001). Positive TNF-␣ levels (>10 pg/ml) were found in 26% of NSCLC compared to 3% of COPD (P < 0.002) and 5% of controls (P < 0.0005). On the other hand, positive (>8.5 pg/ml) IL-6 levels were found in 53% of NSCLC and 21% of COPD patients, compared to 5% of control subjects (P < 0.001). Median TATc levels were elevated in either NSCLC (6.9 g/l) or COPD (5.7 g/l) patients compared to controls (1.8 g/l, P < 0.0001). Elevated D-dimer levels were significantly associated to positive TNF-␣ levels in patients without distant metastasis (F = 4.3, P < 0.05). Moreover, TNF-␣ levels (P < 0.01) were independently related to the presence of positive D-dimer levels in patients with non-metastatic NSCLC. These results suggest that increased levels of TNF-␣ might be responsible for an activation of fibrinolysis in patients with NSCLC.

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The Role of Cytokines in Activation of Coagulation and Fibrinolysis in Dengue Shock Syndrome

Cited by 101 publications

References 23 publications

Variation in Inflammatory/Regulatory Cytokines in Secondary, Tertiary, and Quaternary Challenges with Dengue Virus

Variation in Inflammatory/Regulatory Cytokines in Secondary, Tertiary, and Quaternary Challenges with Dengue Virus

Dengue Virus-Induced Autoantibodies Bind to Plasminogen and Enhance Its Activation

Correlation between tumor necrosis factor-alpha and d-dimer levels in non-small cell lung cancer patients

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