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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The paroxysms of Plasmodium vivax malaria are antiparasite responses that, although distressing to the human host, almost never impart serious acute pathology. Using plasma and blood cells from P. vivax patients, the cellular and noncellular mediators of these events have been studied ex vivo. The host response during a P. vivax paroxysm was found to involve T cells, monocytes and neutrophils, and the activity, among others, of the pyrogenic cytokines tumor necrosis factor alpha and interleukin 2 in addition to granulocyte macrophage-colony stimulating factor. However, interferon gamma activity, associated with serious acute pathogenesis in other studies on malaria, was absent. Induction of the cytokines active during a P. vivax paroxysm depends upon the presence of parasite products, which are released into the plasma before the paroxysm. Chemical identification of these natural parasite products will be important for our understanding of pathogenesis and protection in malaria.
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PMID:The paroxysm of Plasmodium vivax malaria. 1268 50

It is proposed that the surface ligands of Plasmodium falciparum infected HbAS erythrocytes, not like infected HbAA erythrocytes, are altered due to the sickling that soon takes place once a HbAS erythrocyte gets infected with P. falciparum parasite. This alteration modulates cytoadherence and/or binding of the sickled erythrocytes to the peripheral blood mononuclear cells (PBMCs). Both cytoadherence and binding to PBMCs are responsible for the pathogenesis of malaria. Therefore, subjects of the HbAS genotype experience mild symptoms of malaria. The hypothesis could be tested in vitro by comparing the binding of P. falciparum infected HbAS and HbAA erythrocytes to platelet-endothelial cell adhesion molecule-1 (CD31) and by comparing the levels of tumor necrosis factor (TNF) and interferon gamma (IFN-gamma) following in vitro stimulation of PBMCs by HbAS and HbAA infected erythrocytes.
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PMID:Protection against severe clinical manifestations of Plasmodium falciparum malaria among sickle cell trait subjects is due to modification of the release of cytokines and/or cytoadherence of infected erythrocytes to the host vascular beds. 1269 25

Much of the pathology of malaria is mediated by inflammatory cytokines (such as interleukin 12, interferon gamma, and tumor necrosis factor alpha), which are part of the immune response that kills the parasite. The antiinflammatory cytokine transforming growth factor (TGF)-beta plays a crucial role in preventing the severe pathology of malaria in mice and TGF-beta production is associated with reduced risk of clinical malaria in humans. Here we show that serum-free preparations of Plasmodium falciparum, Plasmodium yoelii 17XL, and Plasmodium berghei schizont-infected erythrocytes, but not equivalent preparations of uninfected erythrocytes, are directly able to activate latent TGF-beta (LatTGF-beta) in vitro. Antibodies to thrombospondin (TSP) and to a P. falciparum TSP-related adhesive protein (PfTRAP), and synthetic peptides from PfTRAP and P. berghei TRAP that represent homologues of TGF-beta binding motifs of TSP, all inhibit malaria-mediated TGF-beta activation. Importantly, TRAP-deficient P. berghei parasites are less able to activate LatTGF-beta than wild-type parasites and their replication is attenuated in vitro. We show that activation of TGF-beta by malaria parasites is a two step process involving TSP-like molecules and metalloproteinase activity. Activation of LatTGF-beta represents a novel mechanism for direct modulation of the host response by malaria parasites.
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PMID:Activation of transforming growth factor beta by malaria parasite-derived metalloproteinases and a thrombospondin-like molecule. 1467 96

T cells are important in the immune response to malaria, both for their cytokines and their help for antibody production. To look at the relative importance of these roles, a T-cell receptor (TCR) transgenic mouse has been generated carrying a TCR specific for an epitope of the merozoite surface protein 1 (MSP-1) of the malaria parasite, Plasmodium chabaudi. In adoptive transfer experiments, malaria-specific CD4(+) T cells expand and produce interferon gamma (IFN-gamma) early in infection, but the population contracts quickly despite prolonged persistence of the parasite. MSP-1-specific CD4(+) cells can protect immunodeficient mice from lethal infection; however, the parasite is only completely cleared in the presence of B cells showing that T helper cells are critical. Levels of malaria-specific antibody and the speed of their production clearly correlate with the time of resolution of infection, indicating that a critical threshold of antibody production is required for parasite clearance. Furthermore, T cells specific for a shed portion of MSP-1 are able to provide help for antibody to the protective region, which remains bound to the infected erythrocyte, suggesting that MSP-1 has all of the components necessary for a good vaccine.
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PMID:Malaria-specific transgenic CD4(+) T cells protect immunodeficient mice from lethal infection and demonstrate requirement for a protective threshold of antibody production for parasite clearance. 1589 Jun 89

Changes of serum cytokines including interferon gamma inducible protein-10 (IP-10) chemokine were analyzed in a total of eight vivax malarial patients before and after chemotherapy by immunostaining for human cytokine antibodies attached to membranes. IP-10 was strongly reactive in the period before chloroquine/primaquine combined chemotherapy and disappeared after chemotherapy in all patients. Therefore, IP-10 chemokine may be of importance in the pathogenesis of vivax malaria and a good marker of a complete cure.
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PMID:Changes of serum cytokine profiles in Korean vivax malarial patients after chemotherapy. 1683

The pro-inflammatory cytokine tumour necrosis factor alpha (TNF-alpha) is associated with malaria virulence (disease severity) in both rodents and humans. We are interested in whether parasite genetic diversity influences TNF-mediated effects on malaria virulence. Here, primary infections with genetically distinct Plasmodium chabaudi chabaudi (P.c.c.) clones varied in the virulence and cytokine responses induced in female C57BL/6 mice. Even when parasitaemia was controlled for, a greater day 7 TNF-alpha response was induced by infection with more virulent P.c.c. clones. Since many functions of TNF-alpha are exerted through TNF receptor 1 (TNFR1), a TNFR-1 fusion protein (TNFR-Ig) was used to investigate whether TNFR1 blockade eliminated clone virulence differences. We found that TNFR-1 blockade ameliorated the weight loss but not the anaemia induced by malaria infection, regardless of P.c.c. clone. We show that distinct P.c.c. infections induced significantly different plasma interferon gamma (IFN-gamma), interleukin 6 (IL-6) and interleukin 10 (IL-10) levels. Our results demonstrate that regardless of P.c.c. genotype, blocking TNFR1 signalling protected against weight loss, but had negligible effects on both anaemia and asexual parasite kinetics. Thus, during P.c.c. infection, TNF-alpha is a key mediator of weight loss, independent of parasite load and across parasite genotypes.
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PMID:Parasite genetic diversity does not influence TNF-mediated effects on the virulence of primary rodent malaria infections. 1697 51

Malaria vaccines aim to induce long lasting protective immunity. Bejon and colleagues propose that levels of rapidly induced (effector memory) interleukin-2 and interferon gamma producing T-cells after vaccination with leading pre-erythrocytic stage vaccines predict the induction of resting memory responses (central memory). Herein we discuss Bejon's findings in the context of current thinking on the generation and maintenance of T cell memory, with particular emphasis on the role of cytokines.
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PMID:Predicting memory: a prospective readout for malaria vaccines? 1758 93

We investigated associations between markers of damage of vascular endothelial cells (MDVECs) and plasma cytokine levels, hemoglobin level and temperature in individuals with acute uncomplicated malaria, as well as healthy controls, using enzyme linked immunosorbent assay (ELISA) for the presence of soluble endothelial cell adhesion molecule-1 (sE-selectin), circulating granule membrane protein-140 (sP-selectin), circulating thrombomodulin (TM), circulating von Willebrand factor (VWf), interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha). Significant differences were observed between falciparum malaria patients and the healthy people in term of levels of both sE-selectin and TM. The serum levels of sP-selectin and VWf were comparable between the two groups. The levels of both sE-Selectin and TM correlated positively with temperature, levels of IFN-gamma and levels of TNF-alpha; and negatively with hemoglobin levels. Trends of positive correlations were observed between level of sP-selectin or VWf and temperature. Furthermore, sE-selectin levels correlated with vomiting. These data suggest that sE-selectin and TM might be useful markers of endothelium activation in in vivo studies. Moreover, our results highlight the use of both sE-selctin and TM as markers of anemia.
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PMID:Markers of vascular endothelial cell damage and P. falciparum malaria: association between levels of both sE-selectin and thrombomodulin, and cytokines, hemoglobin and clinical presentation. 1877 3

Anemia is a common and serious complication of malaria due to Plasmodium falciparum infection, a major health problem in tropical areas. Herein, the relation was investigated between the levels of circulating erythropoietin (EPO) and immunomodulatory cytokines in response to chloroquine treatment. Thirty-seven healthy control subjects and 40 patients with acute P. falciparum infection were included in the study. All subjects were adult male Sudanese. Blood samples were collected before chloroquine administration (25 mg/kg body weight, orally on three consecutive days) and 3 and 30 days after start of the therapy. Measurements included routine hematological parameters and the concentrations of immunoreactive EPO, tumor necrosis factor-alpha (TNF-alpha), interleukin 1alpha (IL-1), IL-6, and interferon gamma (INF-gamma). Chloroquine treatment led to a decrease in EPO levels in the control subjects but an increase in malaria patients at day 30. The latter was likely due to the anti-inflammatory action of the drug because INF-gamma, IL-1, and IL-6 concentrations declined on chloroquine treatment. Based on these findings, we propose that an impaired EPO production in association with a prolonged elevation of certain inflammatory cytokines can contribute to the anemia in some malaria patients which can be reversed by chloroquine therapy.
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PMID:Effects of chloroquine treatment on circulating erythropoietin and inflammatory cytokines in acute Plasmodium falciparum malaria. 1903 Oct 76

This study aimed to determine the changes in lymphocyte surface markers and cytokine profiles during a malarial infection in a mouse model of malaria. Mononuclear cells obtained from the spleens of the mice infected with Plasmodium berghei (P. berghei) were stained with anti-mouse CD3, anti-mouse CD4, anti-mouse CD8, anti-mouse CD19, anti-mouse CD152, anti-mouse pan natural killer (NK), anti-mouse CD80 monoclonal antibodies and expression of surface markers was evaluated by flow cytometry. In the serum samples of the mice, the levels of tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), transforming growth factor-1beta (TGF-1beta), and interleukin (IL)-4, IL-10, and IL-12 cytokines were determined by ELISA method. The expressions of all the surface markers of lymphocyte evaluated were statistically significantly lower in the infected mice than in the healthy control mice (p < 0.05). However, except for the level of TGF-1beta, the levels of all the other cytokines evaluated were statistically significantly higher in the infected group than in the control group (p < 0.001). No significant differences were determined between the TGF-1beta levels of the study and control groups (p > 0.05). In this study, T, B, and NK lymphocyte responses were inhibited and cytokine profiles changed in the course of malarial infection. Thus, interventions to increase the Th1 lymphocyte response may be beneficial in the prevention of malarial infection.
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PMID:Determination of the expression of lymphocyte surface markers and cytokine levels in a mouse model of Plasmodium berghei. 1984 11


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