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

To determine whether iron chelation modulates nitric oxide (NO) formation and cell-mediated immune effector function in children with cerebral malaria, serum concentrations were measured of the stable end products of NO, nitrite and nitrate (NO2-/NO3-), interleukin (IL)-4, -6, and -10, and neopterin in 39 Zambian children enrolled in a placebo-controlled trial of desferrioxamine B and quinine therapy. Mean concentrations of NO2-/NO3- increased significantly over 3 days in children receiving desferrioxamine plus quinine but not in those given placebo and quinine. Neopterin levels declined significantly with placebo but not with desferrioxamine. IL-4 levels increased progressively in the placebo group and ultimately decreased in the desferrioxamine group, but the trends were not statistically significant. IL-6 and IL-10 levels were elevated initially and decreased significantly in both groups over 3 days. These data are consistent with the hypothesis that iron chelation therapy in children with cerebral malaria strengthens Th1-mediated immune effector function involving increased production of NO.
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PMID:Modulatory potential of iron chelation therapy on nitric oxide formation in cerebral malaria. 898 27

Murine malarial parasites have long been characterized by their requirement for either antibody-mediated immunity (AMI) or cell-mediated immunity (CMI) for suppression of acute parasitemia, with Plasmodium yoelii reportedly requiring AMI for suppression and P. chabaudi requiring CMI. To assess this characterization in terms of the current T(H1)/T(H2)-CMI/AMI hypothesis, we infected gene-targeted "knockout" mice lacking either a type-1 cytokine (IL-2 or IFN-gamma) or a type-2 cytokine (IL-4 or IL-10) with one or the other species of Plasmodium. We observed that type-1 cytokine-deficient mice developed exacerbated malaria with either P. yoelii or P. chabaudi, compared with that seen in heterozygote controls. Moreover, type-2 cytokine knockout mice showed a similar time course of infection with either parasite compared with that seen with their controls. We conclude that the mechanism of resolution of these well characterized malarial infections cannot be linked definitely to these T(H1)- and T(H2)-associated cytokines as predicted by the T(H1)/T(H2)-CMI/AMI hypothesis.
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PMID:The time course of selected malarial infections in cytokine-deficient mice. 903 Jun 70

Mechanisms responsible for the increase in malaria susceptibility during pregnancy, and in particular during the first pregnancy, have not been elucidated. T and B cell responses to leucoagglutinin, bacille Calmette-Guerin (BCG) and to six Plasmodium falciparum antigens were longitudinally investigated in 33 pregnant women during their first pregnancy, after delivery, and during second pregnancy. Parasitological data obtained from the same women during and after the first pregnancy demonstrated the higher risk of P. falciparum infection during this pregnancy. Plasma levels of antibodies to Pf155/ RESA were lower during pregnancy than after delivery. Conversely, antibodies to P. falciparum asexual blood stages were higher during pregnancy than after delivery, suggesting that during pregnancy the regulation of antibody production may be variously impaired depending upon the antigens. The most striking finding of the present study is the impairment of the IL-2 cellular response during the first pregnancy. Conversely, proliferative responses, as well as IL-4 and interferon-gamma (IFN-gamma) responses, were either unaffected or moderately enhanced. No difference in humoral and cellular responses was observed between first and second pregnancy. The impairment of the IL-2 responses involved the response to malaria peptides and proteins, as well as the response to non-malarial antigens and to the mitogen leucoagglutinin. Thus, the alteration of malaria immunity might rather fall into the general frame of the depression of cellular immunity during pregnancy than involve a specific malaria phenomenon.
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PMID:Immune response to Plasmodium falciparum antigens in Cameroonian primigravidae: evolution after delivery and during second pregnancy. 906 18

This study investigates the effect of orally administered testosterone on serum testosterone levels and immune responses including outcome of Plasmodium chabaudi malaria. Female C57BL/10 mice were fed on a diet impregnated with 17 alpha-methyl-testosterone for 3 weeks. This raised the circulating testosterone levels from 0.28 ng/ml to 2.69 ng/ml on the average. In these mice, blood-stage infections of P. chabaudi resulted in a lethal outcome, whereas protective immunity developed in about 80% of mice fed on control diet without testosterone. Dietary 17 alpha-methyl-testosterone reduced the capacity of peritoneal cells to generate reactive oxygen intermediates after stimulation with C3b-coated zymosan and phorbol-myristate-acetate. Also, mice fed on dietary 17 alpha-methyl-testosterone responded to heat-killed Salmonella typhimurium with a higher increase in serum TNF, whereas the induced increase in the production of IL-10 by spleen cells was largely suppressed and no effect was found with respect to the production of IFN-gamma and IL-4. Our data indicate that the method of oral administration of 17 alpha-methyl-testosterone raises circulating testosterone to levels that impair protective immune responses to P. chabaudi malaria.
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PMID:Dietary testosterone suppresses protective responsiveness to Plasmodium chabaudi malaria. 907 23

Fatal murine cerebral malaria (FMCM) is an immunopathological process. The depletion of CD4+ T cells, or the administration of antioxidants or antibodies against certain cytokines, protect the mice against cerebral complications. We previously have shown that astrocytes, microglia, and monocytes play a role in the development of FMCM, suggesting that an active immune response occurs locally within the central nervous system. We now have investigated the functional involvement of glia and monocytes in FMCM by assessing 1) the production, 2) the temporal appearance, and 3) the cellular source of cytokine mRNA and protein in the brain. Brain sections from uninfected and FMCM mice were analyzed for the presence of cytokine mRNA and protein by in situ hybridization and immunohistochemistry. Tumor necrosis factor (TNF)-alpha mRNA and protein were associated with microglia and astrocytes, monocytes, and the cerebral vascular endothelium in FMCM mice but not uninfected animals. TNF-alpha mRNA was first detected several days before the animals showed cerebral symptoms and died. Interleukin (IL)-1 beta mRNA was found in the brains of both uninfected and FMCM mice. However, IL-1 beta protein was associated only with monocytes, the meningeal vascular endothelium, and neurons in the fronto-parietal cortex in the FMCM brains. No IL-4 or IL-6 mRNAs were detected in either group. These results provide the strongest evidence to date that cytokines, in particular TNF-alpha, produced locally in the central nervous system play a role in the pathogenesis of FMCM.
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PMID:Tumor necrosis factor-alpha expression in the brain during fatal murine cerebral malaria: evidence for production by microglia and astrocytes. 909 2

The reverse transcriptase-polymerase chain reaction (RT-PCR) was used to amplify selected lymphokine mRNAs from phytohemagglutinin-activated leukocytes of the owl monkey (Aotus trivirgatus). Interleukin-2 (IL-2), IL-4, IL-13, and interferon-gamma were selected as lymphokine mRNAs of interest, since expression of these cytokines helps define the type of T helper lymphocyte response (i.e., TH1 versus TH2). Because sequences for these lymphokine genes were not available for the owl monkey, multiple PCR primers for each lymphokine gene were designed based on published human sequences. Various PCR primer pairs were then used in the RT-PCR to determine the conditions for optimal amplification of each owl monkey cytokine mRNA. In addition, each PCR primer pair was compared for the ability to amplify lymphokine mRNAs from other primate species, including African green (Cercopithecus aethiops), squirrel (Saimiri sciureus), and rhesus (Macaca mulatta) monkeys. The specificity and sensitivity of optimal primer pair was also demonstrated by amplification of as little as 10 fg of each lymphokine gene in a background of 300 ng of irrelevant cDNA. Finally, partial sequences of owl monkey coding regions for IL-2, IL-13, and interferon-gamma were determined and compared for homology with their human counterparts. Together, these studies define specific and sensitive conditions for detection of lymphokine mRNA expression in the owl monkey and provide partial sequence information of the coding region for these lymphokines. This investigation should provide molecular probes to investigate the immune response against malaria and the effectiveness of malaria vaccines in the owl monkey that models this human disease.
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PMID:Reverse transcriptase-polymerase chain reaction amplification and partial sequence of T helper 1- and T helper 2-type lymphokine genes from the owl monkey (Aotus trivirgatus). 912 42

A prospective study in 207 children aged 0.5-15 years was carried out in a highly endemic area of Papua New Guinea to examine the relationship between cellular responses to Plasmodium falciparum merozoite surface protein 2 (MSP2) and malaria infection and morbidity. In vitro proliferation, IFN-gamma and IL-4 induction were measured against two recombinant proteins of MSP2, FC27 and 3D7 as well as against a form of the 3D7 MSP2 lacking the central repetitive sequences (d3D7). The prevalence of proliferative response was generally low, 6% for FC27, 9% for 3D7 and 11% for d3D7. A higher prevalence of IL-4 response was obtained being 27% for FC27, 34% for 3D7 and 30% for d3D7 while the prevalence of IFN-gamma response was 13%, 15% and 18%, respectively. There was no correlation between age and proliferative responses; in contrast cytokine production increased with age for all three antigens. When proliferation or stimulation of either cytokine was used to assess T-cell activation the frequency of responders increased to 39%, 47% and 46% for FC27, 3D7 and d3D7 respectively. Analysis of the relation of T cell responses to concurrent infection and morbidity showed that lymphoproliferative response only to d3D7 was significantly associated with parasitaemia; while lymphoproliferative responses to all 3 MSP2 antigens were highest in the group of clinical malaria cases. There was no significant correlation between proliferation or cytokine production to MSP2 and concurrent or subsequent malaria morbidity.
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PMID:Cellular immunity to merozoite surface protein 2 (FC27 and 3D7) in Papua New Guinean children. Temporal variation and relation to clinical and parasitological status. 919 97

People living in Plasmodium falciparum-endemic areas frequently have elevated levels of total as well as P. falciparum-specific serum IgE. This study aimed at investigating whether the elevated serum IgE levels reflect a shift in the balance between CD4+ T helper 1 (Th1) and T helper 2 (Th2) cells in individuals naturally exposed to the P. falciparum parasite. To investigate the role of Th1 and Th2 cells in the human P. falciparum system we used the ELISPOT assay to determine the ratio of IFN-gamma- and IL-4-producing cells after specific antigen or mitogen activation in vitro. The donors were individuals who had acquired immunity through natural exposure to the parasite. In response to the specific malaria antigens, very few IL-4-producing cells were seen. However, in the response of individual donors to the polyclonal T cell activator, leucoagglutinin (La), the anti-malarial IgE levels in plasma were correlated with an increased ratio of IL-4/IFN-gamma producing cells. Thus, donors with ratios of IL-4/IFN-gamma > 1 exhibited mean plasma anti-malarial IgE levels significantly greater than those with ratios < 1. In individuals not living in P. falciparum-endemic areas the ratio of IL-4/IFN-gamma was always < 1. Taken together, our data suggest a shift in the balance between Th1 and Th2 cells in naturally P. falciparum-primed individuals, associated with elevated anti-P. falciparum plasma IgE levels. The role and biological significance of IgE (Th2-type immune response) for protection against P. falciparum and/or pathogenesis of malaria require further study.
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PMID:Elevated plasma levels of IgE in Plasmodium falciparum-primed individuals reflect an increased ratio of IL-4 to interferon-gamma (IFN-gamma)-producing cells. 921 29

T cell responses to leucoagglutinin, PPD, and seven Plasmodium falciparum blood stages antigens were investigated in 164 cord blood samples from Cameroonian neonates. In vitro T cell responses were measured by lymphocyte proliferation, and IL-2, IFN-gamma, and IL-4 release in the presence of crude schizont extract, purified Pf155/RESA protein, and synthetic peptides from Pf155/ RESA. Following culture in presence of leucoagglutinin or PPD, proliferation and cytokine production were very low, as compared to adults from the same area. Interestingly, following stimulation of cord blood lymphocytes by malaria antigens, the percentage of responders and the mean level of positive responses were of the same order than those observed in adults for IL-2 production, while proliferative and IL-4 responses were only marginally decreased. Conversely, IFN-gamma production was highly reduced, as compared to adults. Our results demonstrate that prenatal immune priming to malarial antigens is common in this area and that the fetal immune system is able to respond to antigenic stimuli, as cells proliferate and generate cytokines. As cord blood lymphocytes may be induced to differentiate into effector cells producing predominantly Th1 or Th2 cytokines, malaria during pregnancy might direct the functional capacity of fetal T cells to respond to further infection.
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PMID:Malaria cellular immune responses in neonates from Cameroon. 922 85

In tropical areas where Plasmodium falciparum malaria is endemic, concurrent HIV infection does not appear to increase malaria prevalence. To investigate the immunologic interactions between these two infections, 66 adults from Bobo Dioulasso, Burkina Faso, were enrolled in a study in May 1994. The group included 29 HIV-negative adults and 37 hospitalized HIV-positive adults with clinical AIDS and under 250 CD4+ cells per mcgl of blood. All subjects belonged to a population exposed to numerous falciparum malaria infections since birth and were thus presumed to have developed specific antimalarial protective immune mechanisms prior to HIV infection. AIDS patients had a reduced hemoglobin content and a lower number of CD3+ and CD4+ lymphocytes than healthy controls. All thick blood smears were negative for malaria parasites, but the mean level of antibodies to P. falciparum was lower and the total immunoglobulin G content of plasma was higher in AIDS patients than controls. In vitro lymphocyte proliferation and cytokine (IFN-psi, IL-2, and IL-4) production were assessed in isolated mononuclear cells (PBMC) in the presence of PHA, PPD, or 3 antimalarial agents: the baculovirus-expressed protein from P. falciparum Merozoite Surface Protein-1, a P. falciparum in vitro culture, and a crude schizont extract. AIDS patients presented with decreased levels of cell proliferation and of IFN-psi and IL-2 production compared to healthy controls in response to all antigens except the schizont extract. IL-4 production levels were similar in both groups. Mitogenic stimulation of whole blood cultures revealed similar trends in cytokine production as in PBMC cultures. These findings confirm that not all effector cells involved in the immune responses directed against malaria are affected by concurrent HIV infection and/or that important CD4+ independent mechanisms of protection against malaria are conserved. It has been proposed that HIV infection causes a selective depletion of T cell subsets that are not implicated in the antimalarial immune response.
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PMID:Selected P. falciparum specific immune responses are maintained in AIDS adults in Burkina Faso. 922 86


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