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

The intracellular protozoan Plasmodium sp induces a complex immune response which sometimes implies serious pathological effects for the host. According to in vitro studies and epidemiological surveys, several effector mechanisms are displayed against plasmodial blood stages and a large interaction between humoral and cell-mediated immunity is presumed to occur among protected individuals. The key role of T cells in the antiplasmodial immune response is now well established, but all the regulatory heterogenous mechanisms are not yet fully known. An increasing body of data shows a dual role during malaria attack for some cytokines released by monocytes and macrophages (TNF, IL-1, IL-6) or by T cells (IFN-gamma, lymphotoxin (LT), IL-4). The importance of some plasmodial proteins in the cytokine-induced pathology and the stimulation of a preferential TH1 or TH2 mediated immune response to achieve protective immunity against Plasmodium sp are discussed.
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PMID:Cytokines and T-cell response in malaria. 791

To investigate the pathogenic versus the protective role of cytokines and toxin-binding factors in Plasmodium falciparum infections, we measured the concentrations of tumor necrosis factor alpha, interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-1 receptor antagonist, and IL-6, as well as soluble receptors of tumor necrosis factor and IL-6 (sIL-6R) in serum of Gambian children with cerebral malaria, mild or asymptomatic malaria, or other illnesses unrelated to malaria. Because cytokine secretion may be triggered by toxic structures containing phosphatidylinositol (PI), we also measured concentrations of anti-PI antibodies and the PI-binding serum protein beta-2-glycoprotein I. We found increased concentrations of IL-6, sIL-6R, IL-1ra, and some immunoglobulin M antibodies against PI in children with cerebral malaria, but those who died had decreased concentrations of beta-2-glycoprotein I. We conclude that increased concentrations of cytokines and soluble cytokine receptors represent a normal host response to P. falciparum infections but that excessive secretion of cytokines like IL-6 may predispose to cerebral malaria and a fatal outcome while beta-2-glycoprotein I may protect against a fatal outcome of cerebral malaria.
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PMID:Increased concentrations of interleukin-6 and interleukin-1 receptor antagonist and decreased concentrations of beta-2-glycoprotein I in Gambian children with cerebral malaria. 792 98

High levels of interleukin 1 alpha (IL-1 alpha) were detected in vitro, in murine peritoneal macrophages stimulated with Plasmodium vinckei exogenous antigens, and in vivo, in sera of P. vinckei-parasitized mice. Moreover, high production of IL-1 alpha mRNA could be detected by in situ hybridization analysis in spleen sections of mice during the course of P. vinckei malaria. The observed IL-1 alpha gene expression in the spleen was associated with the accumulation of F4/80+ macrophages in the red pulp and in the marginal zone of follicles, as well as with the relative proportions of Mac-1+ cells in the spleen and the capacity of spleen cells to produce reactive oxygen intermediates during murine malaria.
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PMID:Splenic interleukin 1 gene expression is associated with accumulation of macrophages and oxygen radical production in Plasmodium vinckei malaria. 796 3

IL-10 is a monocyte/lymphocyte derived cytokine which has been shown to inhibit certain cellular immune responses such as delayed hypersensitivity. In particular, the production of tumour necrosis factor (TNF), IL-1 and IL-6, which are involved in malaria pathology, are strongly inhibited by IL-10. Accordingly, we examined whether IL-10 could be involved in a human acute parasitic infection such as Plasmodium falciparum malaria. Human IL-10 levels in plasma were determined by two-site ELISA method, taking care to avoid non-specific reactions due to autoantibodies. Fourteen cerebral, 11 severe, and 20 mild malaria cases had mean IL-10 levels of 2812, 2882 and 913 pg/ml, respectively, while 98% of healthy individuals had undetectable (less than 100 pg/ml) circulating IL-10. Thirteen of the 25 cerebral/severe cases had > 2000 pg/ml. In 11 hospitalized patients, circulating IL-10 levels were found to return to virtually normal levels 7 days after antimalarial chemotherapy when biological and clinical malaria features had disappeared (mean levels fell from 3880 to 333 pg/ml). Further studies are required to determine whether these elevated levels of IL-10 play a beneficial role by reducing the parasite-induced inflammatory response, or a detrimental one by decreasing the cellular immune responses.
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PMID:High levels of circulating IL-10 in human malaria. 830 5

In this study, we have identified a dominant glycolipid toxin of Plasmodium falciparum. It is a glycosylphosphatidylinositol (GPI). The parasite GPI moiety, free or associated with protein, induces tumor necrosis factor and interleukin 1 production by macrophages and regulates glucose metabolism in adipocytes. Deacylation with specific phospholipases abolishes cytokine induction, as do inhibitors of protein kinase C. When administered to mice in vivo the parasite GPI induces cytokine release, a transient pyrexia, and hypoglycemia. When administered with sensitizing agents it can elicit a profound and lethal cachexia. Thus, the GPI of Plasmodium is a potent glycolipid toxin that may be responsible for a novel pathogenic process, exerting pleiotropic effects on a variety of host cells by substituting for the endogenous GPI-based second messenger/signal transduction pathways. Antibody to the GPI inhibits these toxic activities, suggesting a rational basis for the development of an antiglycolipid vaccine against malaria.
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PMID:Signal transduction in host cells by a glycosylphosphatidylinositol toxin of malaria parasites. 841 96

To investigate the effect of the heme moiety of malaria pigment, hemozoin, on phagocyte functions, mouse macrophages were fed with insoluble beta-hematin, the synthetic heme-polymer chemically identical to the native pigment, or the soluble monomer, hematin. Production of inflammatory cytokines, interleukin 1 (IL1), tumor necrosis factor alpha (TNF alpha), and nitric oxide (NO) was assayed in the supernatants after stimulation with lipopolysaccharide. The results indicate that both beta-hematin and hematin induce a dose-dependent inhibition of macrophage production of TNF alpha and NO, but not of IL1. One-hour pretreatment with soluble hematin inhibited production of cytotoxic mediators by more than 50% compared to controls, while 6-hr exposure was necessary for insoluble beta-hematin to induce the same level of inhibition. However, the same treatment did not modify the production of TNF alpha and NO by mouse microglia cell lines. The inhibition was partially counterbalanced by adding sulphydryl group donors such as 2-mercaptoethanol, glutathione, or N-acetyl-cysteine during the preincubation time. The results of the present study confirm the inhibitory role of malaria pigment and show that such effect is due to the heme moiety and may be selective for the production of cytotoxic mediators by specific phagocytes. The implications of these findings in the control of malaria infection and disease and in the pathogenesis of severe malaria are discussed.
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PMID:The heme moiety of malaria pigment (beta-hematin) mediates the inhibition of nitric oxide and tumor necrosis factor-alpha production by lipopolysaccharide-stimulated macrophages. 854 91

The scientific interest in the physical interaction of Plasmodium falciparum-infected erythrocytes with host cells stems from the suggestion that excessive binding in the microvasculature leads to severe malaria. The authors studied, therefore, two parasites for their ability to adhere to normal human cells and to induce cytokine production, one parasite lacking a binding capacity (DD2) and one which adhered to CD36+ transfected CHO cells (MCAMP). The MCAMP parasites readily bound to platelets and erythrocytes and to monocytes, polymorphonuclear granulocytes and EBV-transformed B cells as seen by light and electron microscopy. Platelets were frequently attached in large numbers to the infected erythrocyte surface and groups of infected erythrocytes were sometimes held together by several platelets. Nine out of 17 cytokines tested were found to be secreted into the culture supernatants after 35 h of co-cultures containing monocytes or unfractionated peripheral blood mononuclear cells (PBMC) and parasites (IL-1RA, IL-6, IL-8, IL-10, TGF beta, TNF alpha, G-CSF, IL-1-beta, and GM-CSF). Three additional cytokines were also present in low levels (< 200 pg/ml, IL-2, IL-4, IFN gamma) in the culture supernatants after incubation of the cells for 4 days. TNF alpha, IL-RA, and IL-8 were secreted from polymorphonuclear granulocytes, LGLs and T cells. Platelets and, to a lesser degree, monocytes and T cells secreted large amounts of TGF beta (10-30 ng/ml). Cytokines may participate in the pathogenesis but also the suppression of immune responses seen during acute malarial infections.
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PMID:Adhesion of Plasmodium falciparum-infected erythrocytes to human cells and secretion of cytokines (IL-1-beta, IL-1RA, IL-6, IL-8, IL-10, TGF beta, TNF alpha, G-CSF, GM-CSF. 855 86

Intercellular adhesion molecule-1 and E-selectin levels were increased in the plasma of 60 falciparum malaria patients and were not related to levels of tumor necrosis factor alpha, interleukin 10, or interleukin 1 alpha. Soluble E-selectin was correlated to disease; its level in plasma was related to levels of both tumor necrosis factor soluble receptors and biological markers of disease severity and returned to baseline after parasite clearance faster than that of soluble intercellular adhesion molecule-1.
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PMID:Soluble intercellular adhesion molecule-1 and E-selectin levels in plasma of falciparum malaria patients and their lack of correlation with levels of tumor necrosis factor alpha, interleukin 1 alpha (IL-1 alpha), and IL-10. 855 30

In this study we demonstrate that glycosylphosphatidylinositol (GPI) of malaria parasite origin directly increases cell adhesion molecule expression in purified HUVECs in a dose- and time-dependent manner, resulting in a marked increase in parasite and leukocyte cytoadherence to these target cells. The structurally related glycolipids dipalmitoyl-phosphatidylinositol and iM4 glycoinositolphospholipid of Leishmania mexicana had no such activity. Malarial GPI exerts this effect by activation of an endogenous GPI-based signal transduction pathway in endothelial cells. GPI induces rapid onset tyrosine phosphorylation of multiple intracellular substrates within 1 min of addition to cells in a dose-dependent manner. This activity can be blocked by the protein tyrosine kinase-specific antagonist herbimycin A, genistein, and tyrphostin. These tyrosine kinase antagonists also inhibit GPI-mediated up-regulation of adhesion expression and parasite cytoadherence. GPI-induced up-regulation of adhesion expression and parasite cytoadherence can also be blocked by the NF kappa B/c-rel antagonist pyrrolidine-dithiocarbamate, suggesting the involvement of this family of transcription factors in GPI-induced adhesin expression. The direct activation of endothelial cells by GPI does not require the participation of TNF or IL-1. However, GPI is also responsible for the indirect pathway of increased adhesin expression mediated by TNF and IL-1 output from monocytes/macrophages. Total parasite extracts also up-regulate adhesin expression and parasite cytoadherence in HUVECs, and this activity is blocked by a neutralizing mAb to malaria GPI, suggesting that GPI is the dominant agent of parasite origin responsible for this activity. Thus, a parasite-derived GPI toxin activates vascular endothelial cells by tyrosine kinase-mediated signal transduction, leading to NF kappa B/c-rel activation and downstream expression of adhesins, events that may play a central role in the etiology of cerebral malaria.
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PMID:Glycosylphosphatidylinositol toxin of Plasmodium up-regulates intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin expression in vascular endothelial cells and increases leukocyte and parasite cytoadherence via tyrosine kinase-dependent signal transduction. 859 41

After 4 hours of stimulation of human mononuclear leukocytes in the presence of 300 ng/ml exogenous Plasmodium falciparum antigens, the ICAM-1 expression increased variably from 15% to 375%. Simultaneously, an increase of IL-1 mRNA production could be observed in Northern blot hybridizations with a specific cDNA gene probe for human IL-1 alpha labelled with digoxigenin. Furthermore, the reactive oxygen intermediates (ROI) production was also found to be enhanced in similar conditions. Additionally, when the levels of soluble ICAM-1 (sICAM-1) in plasma of 122 patients with P. falciparum or Plasmodium vivax malaria were analyzed in an enzyme immunoassay (EIA), significant sICAM-1 increases were found, more pronounced in patients with P. falciparum malaria, in comparison with healthy controls and with the same patients 4 weeks after chemotherapy. The presented results indicate that the expression of ICAM-1 may also be upregulated by exogenous Plasmodium antigens besides cytokines like IL-1 during the acute phase of malaria, with subsequently elevated sICAM-1 concentrations in blood.
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PMID:Upregulation of ICAM-1, IL-1 and reactive oxygen intermediates (ROI) by exogenous antigens from Plasmodium falciparum parasites in vitro, and of sICAM-1 in the acute phase of malaria. 859 25


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