Cytokine levels during mild and cerebral falciparum malaria in children living in a mesoendemic area

Baptista, João Pedro; Vanham, Guido; Wéry, M; Marck, E. Van

doi:10.1046/j.1365-3156.1997.d01-355.x

Cited by 28 publications

(25 citation statements)

References 14 publications

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“…In contrast, the transcript level of the cytoprotective heme oxygenase gene (hmox-1) was markedly increased at d6 in ⌬hmgb2 ANKAinfected C57BL/6 mice and was thus consistent with the literature (9-11). Our results showing a lower expression level of il-10 transcripts in the brains of ⌬hmgb2 ANKA-infected C57BL/6 mice diverge from other reports on murine CM that suggested a protective effect for IL-10 in CM (67) but are in accordance with observations in humans that showed an increase in IL-10 in CM patients compared to mild malaria patients (68). Finally, the levels of murine hmgb1 transcripts did not vary in hmgb2-deficient ANKA-and WT P. berghei ANKA-infected mice, in contrast to the murine hmgb2 transcript levels, which were highly increased in P. berghei ANKA-infected mice and remained unchanged in ⌬hmgb2 ANKA-infected mice.…”

Section: Discussionsupporting

confidence: 77%

Disruption of Parasitehmgb2Gene Attenuates Plasmodium berghei ANKA Pathogenicity

et al. 2015

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h Eukaryotic high-mobility-group-box (HMGB) proteins are nuclear factors involved in chromatin remodeling and transcription regulation. When released into the extracellular milieu, HMGB1 acts as a proinflammatory cytokine that plays a central role in the pathogenesis of several immune-mediated inflammatory diseases. We found that the Plasmodium genome encodes two genuine HMGB factors, Plasmodium HMGB1 and HMGB2, that encompass, like their human counterparts, a proinflammatory domain. Given that these proteins are released from parasitized red blood cells, we then hypothesized that Plasmodium HMGB might contribute to the pathogenesis of experimental cerebral malaria (ECM), a lethal neuroinflammatory syndrome that develops in C57BL/6 (susceptible) mice infected with Plasmodium berghei ANKA and that in many aspects resembles human cerebral malaria elicited by P. falciparum infection. The pathogenesis of experimental cerebral malaria was suppressed in C57BL/6 mice infected with P. berghei ANKA lacking the hmgb2 gene (⌬hmgb2 ANKA), an effect associated with a reduction of histological brain lesions and with lower expression levels of several proinflammatory genes. The incidence of ECM in pbhmgb2-deficient mice was restored by the administration of recombinant PbHMGB2. Protection from experimental cerebral malaria in ⌬hmgb2 ANKA-infected mice was associated with reduced sequestration in the brain of CD4؉ and CD8 ؉ T cells, including CD8 ؉ granzyme B ؉ and CD8 ؉ IFN-␥ ؉ cells, and, to some extent, neutrophils. This was consistent with a reduced parasite sequestration in the brain, lungs, and spleen, though to a lesser extent than in wild-type P. berghei ANKA-infected mice. In summary, Plasmodium HMGB2 acts as an alarmin that contributes to the pathogenesis of cerebral malaria.

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Section: Discussionsupporting

confidence: 77%

Disruption of Parasitehmgb2Gene Attenuates Plasmodium berghei ANKA Pathogenicity

et al. 2015

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“…the Gambia and Mali in Africa, Madagascar, Gulf of Guinea, and Vietnam. [7][8][9][32][33][34] Most of these studies had cerebral malaria patients as well as severe, non-cerebral patients, who had comparable cytokine levels, whereas the present study had a majority of severe, non-cerebral patients. In Gambia, the cerebral patients who had fatal outcomes had higher TNF-alpha levels (269 pg/ml) 7 which were comparable to those observed in SM patients in the present study.…”

Section: Discussionmentioning

confidence: 80%

Association of high plasma TNF-alpha levels and TNF-alpha/IL-10 ratios with TNF2 allele in severeP. falciparummalaria patients in Sri Lanka

Perera

Herath

Pathirana

et al. 2013

Pathogens and Global Health

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Plasma levels of pro-and anti-inflammatory cytokines of Plasmodium falciparum-infected patients with severe malaria (SM; n562) and uncomplicated malaria (UM; n569) from Sri Lanka were assessed. SM patients had significantly higher levels of TNF-alpha (P,0.01), IL-6 (P,0.01), and IL-10 (P,0.05) compared to the UM patients. Plasma IL-2 levels of these patients were undetectable. TNF-alpha levels of a third group of patients with uncomplicated P. falciparum malaria, who were recruited during their fever episodes (UMF; n514) were significantly higher than those of the UM patients (P,0.001) and comparable to SM patients. Plasma IFN-gamma levels of SM patients were higher compared to UM patients, but was not statistically significant. Body temperature in both SM and UMF groups were significantly higher compared to UM group, whereas percentages of parasitemia in all three groups were comparable. Analysis of plasma TNF-alpha levels and the ratio of TNF-alpha/IL-10 in UM (n534) and SM (n534) patients carrying TNF1 and TNF2 allelic types showed that SM patients carrying TNF2 had significantly higher TNFalpha levels as well as TNF-alpha/IL-10 ratio compared to UM patients carrying TNF1, UM patients carrying TNF2 and SM patients carrying TNF1 (P,0.05). These results suggest that the high circulating TNF-alpha levels and the inadequate IL-10 response in the SM patients carrying TNF2 allele could have contributed to the development of severe falciparum malarial disease.

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“…Whereas several case-control studies found higher plasma IFN-␥ levels in SM compared with UM patients [122][123][124][125][126], various similar studies have found higher plasma levels of TNF-␣ [120,[127][128][129][130], IL-2R [131], IL-6 [127,132], IL-1␣ [128], or IL-1␤ [130] but never IFN-␥ in SM compared with UM patients. Furthermore, plasma levels of IL-12 [130,[133][134][135][136] and IL-18 [134 -136], which induce IFN-␥, have been found to be lower in SM than UM patients.…”

Section: Evidence For Ifn-␥ In Inflammation and Immunopathologymentioning

confidence: 99%

Interferon-γ—central mediator of protective immune responses against the pre-erythrocytic and blood stage of malaria

McCall

Sauerwein

2010

Journal of Leukocyte Biology

137

113

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Immune responses against Plasmodium parasites, the causative organisms of malaria, are traditionally dichotomized into pre-erythrocytic and blood-stage components. Whereas the central role of cellular responses in pre-erythrocytic immunity is well established, protection against blood-stage parasites has generally been ascribed to humoral responses. A number of recent studies, however, have highlighted the existence of cellular immunity against blood-stage parasites, in particular, the prominence of IFN-γ production. Here, we have undertaken to chart the contribution of this prototypical cellular cytokine to immunity against pre-erythrocytic and blood-stage parasites. We summarize the various antiparasitic effector functions that IFN-γ serves to induce, review an array of data about its protective effects, and scrutinize evidence for any deleterious, immunopathological outcome in malaria patients. We discuss the activation and contribution of different cellular sources of IFN-γ production during malaria infection and its regulation in relation to exposure. We conclude that IFN-γ forms a central mediator of protective immune responses against pre-erythrocytic and blood-stage malaria parasites and identify a number of implications for rational malaria vaccine development.

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Cytokine levels during mild and cerebral falciparum malaria in children living in a mesoendemic area

Cited by 28 publications

References 14 publications

Disruption of Parasitehmgb2Gene Attenuates Plasmodium berghei ANKA Pathogenicity

Disruption of Parasitehmgb2Gene Attenuates Plasmodium berghei ANKA Pathogenicity

Association of high plasma TNF-alpha levels and TNF-alpha/IL-10 ratios with TNF2 allele in severeP. falciparummalaria patients in Sri Lanka

Interferon-γ—central mediator of protective immune responses against the pre-erythrocytic and blood stage of malaria

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