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

The cytokine tumor necrosis factor and other as yet unidentified factor(s) which together mediate the killing of intraerythrocytic malaria parasites are transiently elevated in sera during paroxysms in human Plasmodium vivax infections in non-immunes. These factors which included TNF and parasite killing factor(s) are associated with the clinical disease in malaria to the extent that their transient presence in infection sera coincided with paroxysms, the the most pronounced clinical disturbances of P. vivax malaria and secondly because their levels were markedly lower in paroxysm sera of semi-immune patients who were resident of an endemic area. Further, a close parallel was obtained between serum TNF levels and changes in body temperature that occur during a P. vivax paroxysm in non-immune patients, suggesting a causative role for TNF in the fever in malaria. P. vivax rarely if ever cause complicated clinical syndromes. Nevertheless serum TNF levels reached in acutely ill P. vivax patients were as high as in patients suffering from cerebral complications of P. falciparum malaria as reported in studies from the Gambia. Cytokine profiles and other changes accompanying clinical disease in P. vivax and P. falciparum malaria are compared in this paper with a view to discussing the potential role of cytokines in the causation of disease in malaria.
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PMID:The role of cytokines in Plasmodium vivax malaria. 134 26

Evidence for immune activation was investigated in 12 patients with a rare syndrome of self-limiting, delayed onset cerebellar dysfunction following an attack of falciparum malaria which occurred 18-26 d previously. Concentrations of tumour necrosis factor, interleukin 6 and interleukin 2 were all significantly higher in serum samples of patients during cerebellar ataxia than in recovery sera and in the sera of 8 patients who did not develop delayed cerebellar dysfunction following an attack of falciparum malaria. Cytokine concentrations in the cerebrospinal fluid were also significantly higher in ataxic patients than in controls. These findings suggest that immunological mechanisms may play a role in delayed cerebellar dysfunction following falciparum malaria.
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PMID:Immune activation during cerebellar dysfunction following Plasmodium falciparum malaria. 144 Jul 67

Four antigens of Plasmodium falciparum have so far been identified as targets of transmission-blocking antibodies; three of them (Pfs 230, 48/45) are detectable in gametocytes and expressed on gametes, the fourth (Pfs 25) appears only after fertilization. Epitope analyses of each antigen were made with competitive immunoassays, and the extent of antigenic diversity determined amongst numerous isolates of P. falciparum. There was minimal variation within one of the two epitopes on Pfs 230 both of which induce transmission-blocking antibodies. The epitopes on Pfs 25 to which blocking monoclonal antibodies respond showed a variability amongst different isolates by immunofluorescence which was unexpected in view of sequence data on the molecule. Five epitope regions have been identified on Pfs 48/45 and antibodies to them interact in a complex manner. Antigenic diversity affecting these epitopes was minimal. In P. vivax malaria much greater polymorphism was seen amongst gamete surface antigens. Natural P. falciparum infections induce antibody responses to gametocyte/gamete surface antigens that will suppress infectivity to mosquitoes but these responses may involve reactivity with any of a series of different epitopes, interactions between antibodies, and may be sequential. In P. vivax infections antibody to the sexual stage antigens may suppress or enhance transmission depending on the antibody level. Cytokine production induced by sexual stage antigens may also modulate transmission, by rendering gametocytes non-infective. Experimental studies showed marked MHC-restriction of immune responses to gamete antigens (but not to the Pfs 25 zygote antigen); the evidence from studies in humans is less convincing. Antibody responses to the sexual stage antigens seem to be more frequent in persons who have experienced only one or a few attacks of malaria as opposed to those who have been exposed frequently. Some form of down-regulation may therefore be occurring.
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PMID:Immunity to sexual stages of human malaria parasites: immune modulation during natural infections, antigenic determinants, and the induction of transmission-blocking immunity. 171 27

Tumour necrosis factor (TNF) has been implicated as a mediator of toxicity in a number of infectious diseases, including malaria. We have shown that human and rodent blood-stage parasites liberate heat-stable soluble antigens that induce the release of TNF by activated macrophages in vitro and in vivo, and are toxic to mice made hypersensitive to TNF by D-galactosamine. These antigens induce T-independent antibodies which specifically block their ability, but not that of bacterial lipopolysaccharide, to cause the secretion of TNF. Cytokine release in vitro may be a useful strategy for identifying potentially toxic molecules of infectious organisms and for investigating the nature of antibodies that can protect the host against their damaging effects.
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PMID:Induction of TNF in vitro as a model for the identification of toxic malaria antigens. 267 57

Cytokine regulation was compared in three groups of Gabonese patients with Plasmodium falciparum malaria before and after therapy; adults with uncomplicated malaria, children with uncomplicated malaria, and children with severe malaria. Plasma levels of tumor necrosis factor (TNF), interleukin-6 (IL-6), IL-8, TNF receptors (TNF R), and the TNF/TNF R ratios were significantly higher in severe malaria compared with uncomplicated malaria. High plasma levels of all immunoregulatory molecules were associated with slow cure after therapy. In all patients, phytohemagglutinin-induced cytokine production was depressed on admission compared with convalescence. A significant difference was the higher TNF production capacity in patients with severe malaria on day 2 and day 5 compared with that in patients with uncomplicated malaria. In contrast to IL-6 and IL-8, a high TNF production capacity during the acute phase of malaria predicted a rapid clinical and parasitologic cure in the patients. These findings illustrate the dual role of TNF in the protection and pathology of malaria.
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PMID:Prediction of accelerated cure in Plasmodium falciparum malaria by the elevated capacity of tumor necrosis factor production. 748 13

When murine peritoneal macrophages were loaded in vitro with Plasmodium vinckei hemozoin and stimulated for 24 hours with interferon-gamma and/or Escherichia coli lipopolysaccharide, the production of interleukin 6 (IL-6) was drastically reduced, whereas the secretion of tumor necrosis factor (TNF) was increased. In addition, non-radioactive in situ hybridizations in spleen sections of P. vinckei infected mice showed more TNF than IL-6 gene expression in the red pulp around hemozoin accumulation. These results provide evidence that IL-6 and TNF are differentially modulated by hemozoin and that subsequently, the secretion of IL-6 seems to be independent of the TNF production during murine malaria.
Eur Cytokine Netw
PMID:Hemozoin differentially modulates the production of interleukin 6 and tumor necrosis factor in murine malaria. 757 88

T- and B-cell responses to the Plasmodium falciparum blood-stage antigen Pf155/RESA were investigated in 104 Cameroonian women, half of whom were pregnant. We used purified protein and six synthetic peptides representing T- and B-cell epitopes. In vitro T-cell responses were measured by proliferation and IL2, IFN-gamma, and IL4 release. B-cell responses were assessed by plasma antibodies. All peptides induced a cellular response in some individuals. A proliferative response was induced in 25% of the donors by Pf155/RESA, and in 7 to 11% by any peptide. Cytokine release occurred in 23 to 30% of the Pf155/RESA-stimulated cultures, and in 8 to 25% of the peptide-stimulated cultures. Overall, each peptide induced a cellular response (proliferation and/or cytokine release) in 44% of the donors. T-cells from 23% of the donors failed to respond to any peptide. Responding cells did not usually respond in all readouts, and proliferation and release of any of the three cytokines were not correlated. Similarly, antibody and T-cell responses were not related. Selected epitopes of Pf155/RESA, an important vaccine candidate, are well recognized in naturally exposed individuals and are able to activate T-cells to proliferate and to produce various lymphokines in numerous individuals from a malaria endemic area.
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PMID:Humoral and cellular immune responses to synthetic peptides from the Plasmodium falciparum blood-stage antigen, Pf155/RESA, in Cameroonian women. 761 35

The development of antidisease immunity in children infected with Plasmodium falciparum is thought to be related to their immunologic responses to certain soluble parasite-derived exoantigens. We have assessed both cellular and humoral responses to these antigens in a cross-sectional study of a cohort of Gabonese schoolchildren who live in an area where malaria is holoendemic and perenially transmitted, in an attempt to identify immunologic markers of this early developing protective immunity. Concurrent parasitemia was found to have a significant influence on lymphoproliferative and antibody responses to the exoantigens. Individuals with higher levels of parasitemia had significantly lower proliferative and IgG isotype responses. Higher concentrations of specific IgG1 and IgG3, in particular, were associated with lower or no parasitemia, suggesting a possible protective role for these isotypes, whereas the level of IgM antibodies showed a trend towards higher concentrations in those with parasitemia, perhaps indicative of an exoantigen-induced T cell-independent response. Cytokine responses were unaffected by either the presence or the intensity of parasitemia and were dissociated from both proliferative and antibody response to the exoantigens. However, the mitogen-stimulated production of tumor-necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL)-6 was positively correlated with the corresponding lymphoproliferative responses. At the individual level, mitogen-stimulated TNF-alpha, interferon-gamma, IL-2, and IL-6 responses were positively correlated, as were mitogen- and exoantigen-induced TNF-alpha. The results are discussed in the light of current knowledge of immune responses to the exoantigens and the development of protective immunity to P. falciparum.
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PMID:Immunologic responses to soluble exoantigens of Plasmodium falciparum in Gabonese children exposed to continuous intense infection. 781 Aug 4

Pathogenic mechanisms of brain microvascular injury were studied in an experimental model of cerebral malaria (CM). The lesion, leading to perivascular microhemorrhages, is due to cytokine overproduction, and is associated with the sequestration of macrophages and parasitized erythrocytes in cerebral venules. In this in vivo model, we demonstrate that platelets are critical effectors of the neurovascular injury. First, electron microscopy indicated that during CM platelets adhere to and probably damage brain endothelial cells. Second, radiolabelled platelet distribution studies indicated that platelets sequestered in the brain and lung vasculature during CM. Non-cerebral malaria was not associated with cerebral sequestration of platelets. Third, in vivo treatment with a mAb to LFA-1 (which is expressed on platelets) selectively abrogated the cerebral sequestration of platelets, and this correlated with prevention of CM. Fourth, malaria-infected animals rendered thrombocytopenic were significantly protected against CM, further indicating that platelets are central to the pathogenesis of CM. Thus, a CD11a-dependent interaction between platelets and endothelial cells appears pivotal to microvascular damage. These data suggest a novel mechanism of action for anti-LFA-1 mAb in vivo and illustrate an unexpected role of platelets, in addition to monocytes, in vascular pathology.
Eur Cytokine Netw
PMID:TNF-induced microvascular pathology: active role for platelets and importance of the LFA-1/ICAM-1 interaction. 791 Apr 90

Plasma from immune (residents of malaria infested areas) and non immune (European travellers) patients suffering from cerebral malaria, severe or mild, was analyzed for the presence of soluble tumor necrosis factor receptors. On admission of the subjects, sTNF-R55 and sTNF-R75 levels were significantly elevated in all groups and correlated with TNF-alpha. Except for sTNF-R55 whose levels were higher in severe than in mild malaria, no correlation was observed between soluble receptors and clinical status. Nevertheless, sTNF-R55 and sTNF-R75 were significantly more elevated in patients who died (10.7 +/- 2.3 ng/ml and 94.9 +/- 31 ng/ml, respectively) than in those surviving (5.5 +/- 0.4 ng/ml and 37.4 +/- 5.4 ng/ml respectively). A marked correlation was observed between soluble receptors levels and some biological markers of gravity like creatinine, urea, and bilirubin. In 13 non immune patients, circulating soluble receptors levels decreased significantly after 7 days when clinical and biological malaria features had disappeared, but TNFsR75 remained above normal levels. After a fortnight of treatment in 17 immune patients, sTNF-R55 and sTNF-R75 remained elevated. However, the ratios of TNF-alpha/s TNF-R55 and 75 were not higher in the cases of cerebral malaria or fatal outcome. Further studies are required to determine if elevated levels of sTNF-R55 and sTNF-R75 are beneficial, due to the inhibition of TNF-alpha or whether they are detrimental since they stabilize this deleterious cytokine.
Eur Cytokine Netw
PMID:Plasma levels of TNF-alpha soluble receptors correlate with outcome in human falciparum malaria. 794 68


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