Prediction of Accelerated Cure in Plasmodium falciparum Malaria by the Elevated Capacity of Tumor Necrosis Factor Production

Kremsner, Peter G.; Winkler, Stefan; Brandts, Christian; Wildling, Eckart; Jenne, Lars; Graninger, Wolfgang; Prada, Javier; Bienzle, Ulrich; Juillard, Pierre; Grau, Georges E.

doi:10.4269/ajtmh.1995.53.532

Cited by 93 publications

(66 citation statements)

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“…Although TNF-α and IL-1β are associated with severe malaria and cerebral malaria in children, 67,68 they are also important for parasite killing during malaria infection. [12][13][14][15][16][69][70][71][72] Similar to other results, the production of TNF-α and IL-1β by infected macrophages increased with LPS and LPS+IFN-γ. These results also consistent with several other studies showing that BCG stimulates the production of TNF-α and IL-1β by macrophages, [73][74][75] and the stimulation is enhanced in the presence of LPS 73 and further enhanced with the presence of LPS+IFN-γ.…”

Section: Discussionsupporting

confidence: 70%

“…[12][13][14] Furthermore, these cytokines have been reported to protect against the development of cerebral malaria and control parasitemia in animal and human models. 15,16 NO, on the other hand has potent parasiticidal properties against P. falciparum 17 and is an important effector in limiting parasitemia. 18 These mechanisms are vital in controlling malaria infection in both animals and humans.…”

Section: Introductionmentioning

confidence: 99%

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Immunomodulatory effects of recombinant BCG expressing MSP-1C ofPlasmodium falciparumon LPS- or LPS+IFN-γ-stimulated J774A.1 cells

Mohamad

Suppian

Nor

2014

Human Vaccines & Immunotherapeutics

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Section: Discussionsupporting

confidence: 70%

Section: Introductionmentioning

confidence: 99%

Immunomodulatory effects of recombinant BCG expressing MSP-1C ofPlasmodium falciparumon LPS- or LPS+IFN-γ-stimulated J774A.1 cells

Mohamad

Suppian

Nor

2014

Human Vaccines & Immunotherapeutics

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“…13 It is, therefore, important to show that neutralizing TNF-␣ does not delay parasite clearance. Three of the groups given Fab had longer parasite clearance values than the control group, but the increases were not dose-related.…”

Section: Discussionmentioning

confidence: 99%

Polyclonal anti-tumor necrosis factor-alpha Fab used as an ancillary treatment for severe malaria.

Looareesuwan

Sjostrom²,

Krudsood³

et al. 1999

The American Journal of Tropical Medicine and Hygiene

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Abstract. Single doses (250, 500, 1,000, or 2,000 units/kg) of an ovine polyclonal-specific Fab fragment directed against tumor necrosis factor-␣ (TNF-␣) were given to 17 adult patients with severe falciparum malaria immediately before treatment with artesunate in a pilot study to assess safety and optimal dosage with a view to future studies. Clinical and laboratory variables were compared with 11 controls. In the groups given Fab, there was a tendency for a faster resolution of clinical manifestations and reduction of fever but also a tendency towards longer parasite clearance times. Adverse events were more common in the control group and no early anaphylactic or late serum sickness reactions occurred in the Fab treated patients. On admission all patients had markedly elevated levels of TNF-␣ (85-1,532 ng/L) and interleukin-6 (IL-6) (30-27,500 ng/L). Also, 86% had elevated interferon-␥ (IFN-␥) levels, 75% had increased IL-2 levels, 36% had increased IL-8 levels, and 21% had increased IL-1␤ levels. Antibody treatment reduced IFN-␥ concentrations in a dose-related manner, but had no obvious effects on levels of other cytokines in this small study, although unbound TNF-␣ was undetectable after Fab treatment. Circulating concentrations of soluble E-selectin, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were not affected by Fab treatment. The Fab exhibited a two-compartment, dose-proportional kinetics with an average elimination halflife of 12.0 hr, with about 20% being excreted renally. These results encourage a randomized, placebo-controlled trial in patients with cerebral malaria and provide some guidance about dosage.

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“…IFN-␥ is the key inducer of the immune effector mechanisms that are essential for initial control of both pre-erythrocytic and blood-stage malaria infections (8,9), but there is evidence that IFN-␥ levels need to be carefully balanced to avoid immune pathology (10,11). In vivo, TNF-␣ production is associated with parasite clearance and resolution of fever (12), but elevated levels of TNF-␣ (13) and IL-6 (14,15) have also been associated with cerebral malaria. A priori, one would expect a crucial role for IL-12-and possibly also IL-18 -in initiation of the inflammatory cytokine cascade.…”

Section: R Esearch On the Immunology Of Malaria Infection Has Beenmentioning

confidence: 99%

Innate Immune Responses to Human Malaria: Heterogeneous Cytokine Responses to Blood-Stage Plasmodium falciparum Correlate with Parasitological and Clinical Outcomes

Walther

Woodruff

Edele

et al. 2006

The Journal of Immunology

141

118

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Taking advantage of a sporozoite challenge model established to evaluate the efficacy of new malaria vaccine candidates, we have explored the kinetics of systemic cytokine responses during the prepatent period of Plasmodium falciparum infection in 18 unvaccinated, previously malaria-naive subjects, using a highly sensitive, bead-based multiplex assay, and relate these data to peripheral parasite densities as measured by quantitative real-time PCR. These data are complemented with the analysis of cytokine production measured in vitro from whole blood or PBMC, stimulated with P. falciparum-infected RBC. We found considerable qualitative and quantitative interindividual variability in the innate responses, with subjects falling into three groups according to the strength of their inflammatory response. One group secreted moderate levels of IFN-γ and IL-10, but no detectable IL-12p70. A second group produced detectable levels of circulating IL-12p70 and developed very high levels of IFN-γ and IL-10. The third group failed to up-regulate any significant proinflammatory responses, but showed the highest levels of TGF-β. Proinflammatory responses were associated with more rapid control of parasite growth but only at the cost of developing clinical symptoms, suggesting that the initial innate response may have far-reaching consequences on disease outcome. Furthermore, the in vitro observations on cytokine kinetics presented here, suggest that intact schizont-stage infected RBC can trigger innate responses before rupture of the infected RBC.

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Prediction of Accelerated Cure in Plasmodium falciparum Malaria by the Elevated Capacity of Tumor Necrosis Factor Production

Cited by 93 publications

References 0 publications

Immunomodulatory effects of recombinant BCG expressing MSP-1C ofPlasmodium falciparumon LPS- or LPS+IFN-γ-stimulated J774A.1 cells

Immunomodulatory effects of recombinant BCG expressing MSP-1C ofPlasmodium falciparumon LPS- or LPS+IFN-γ-stimulated J774A.1 cells

Polyclonal anti-tumor necrosis factor-alpha Fab used as an ancillary treatment for severe malaria.

Innate Immune Responses to Human Malaria: Heterogeneous Cytokine Responses to Blood-Stage Plasmodium falciparum Correlate with Parasitological and Clinical Outcomes

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