Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dietary fish-oil supplementation interferes with eicosanoid production and appears to decrease production of interleukin-1 (IL-1) and tumor necrosis factor (TNF). The effect of fish oil was investigated in an intramuscular Klebsiella pneumoniae infection in Swiss mice and in cerebral malaria induced by Plasmodium berghei in C57B1/6 mice. After a low inoculum of K. pneumoniae, 90% of fish oil-fed mice survived; survival in control mice fed equal amounts of corn or palm oil or normal chow was 30%, 40%, and 0, respectively. Cerebral malaria occurred in only 23% of fish oil-fed mice; in the controls, cerebral malaria developed in 61%, 81%, and 78%, respectively. Contrary to what was expected, lipopolysaccharide-induced ex vivo production of IL-1 alpha and TNF alpha by peritoneal cells was significantly enhanced in fish oil-fed mice compared with controls. Indomethacin treatment did not alter the outcome in these two infections, thus arguing against reduced prostaglandin synthesis as an explanation for the increase in resistance to infection.
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PMID:Dietary fish-oil supplementation in experimental gram-negative infection and in cerebral malaria in mice. 156 40

Cerebral malaria is the most important manifestation of severe Plasmodium falciparum infection. The clinical picture in South East Asian adults differs from that in African children. The children are more likely to have abnormal brain stem reflexes, signs suggestive of cerebral herniation, and raised CSF opening pressure, and to suffer persistent neurological sequelae. The mortality remains high at about 20%. The diagnosis must be considered in all patients with fever and impaired consciousness who may have been exposed to the infection. The pathophysiology of cerebral malaria may involve mechanical obstruction of the cerebral circulation by parasitized erythrocytes which have adhered to the vascular endothelium. Cytokines such as tumor necrosis factor may also contribute. The most important element of treatment is early, optimal chemotherapy with quinine, but artemisinine derivatives may prove even more effective.
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PMID:Cerebral malaria. 161 97

Serum cytokine profiles were evaluated in immunized and nonimmunized human volunteers after challenge with infectious Plasmodium falciparum sporozoites. Three volunteers had been immunized with x-irradiated sporozoites and were fully protected from infection. Four nonimmune volunteers all developed symptomatic infection at which time they were treated. Sera from all volunteers were collected at approximately 20 time points during the 28-d challenge period; levels of IL-1 alpha, IL-1 beta, IL-2, IFN-gamma, tumor necrosis factor-alpha, IL-4, IL-6, granulocyte macrophage-colony-stimulating factor, and soluble CD4, CD8, and IL-2 receptor (sCD4, sCD8, and sIL-2R, respectively) were determined by ELISA. C-reactive protein (CRP) was assayed by radial immunodiffusion. Parasitemic subjects developed increases in CRP and IFN-gamma, with less marked increases in sIL-2R and sCD8; the other cytokines tested did not change. CRP increases were abrupt and occurred at the onset of fever (day 14 after challenge). IFN-gamma increases were also abrupt, preceding those of fever and CRP by one day. Increases in sIL-2R and sCD8 were more gradual. Increases in fever, CRP, IFN-gamma, and sCD8 were concordant in each volunteer. Early IL-6 increases were noted in the protected vaccinees. Thus, after challenge with virulent P. falciparum, unique systemic cytokine profiles were detectable both in immunized, nonparasitemic volunteers and in unvaccinated, parasitemic subjects. The contrasting cytokine profiles in the two groups may relate to mechanisms of protection and immunopathology in experimental human malaria.
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PMID:Serum cytokine profiles in experimental human malaria. Relationship to protection and disease course after challenge. 164 22

We analyzed the role of adhesion molecules in the pathogenesis of experimental cerebral malaria (ECM), since tumor necrosis factor (TNF) plays a major role in this condition and has been shown to up-regulate in vitro expression of cell adhesion molecules (CAM), particularly intercellular CAM-1 (ICAM-1). We found increased expression of ICAM-1 on brain endothelial cells from mice with ECM. Treatment with monoclonal antibodies (mAb) directed against leukocyte function-antigen 1 (LFA-1, the ligand of ICAM-1) on days 6, 8 and 10 almost totally prevented ECM, while decreasing blood TNF levels. To exclude the possibility that the effects of anti-LFA-1 mAb resulted from an even partial inhibition of TNF overproduction, mice with signs of imminent death (hypothermia and neurologic defects) were treated with the anti-LFA-1 mAb, with dramatically protective effect. In contrast, injection of anti-ICAM-1 mAb on day 6 caused rapid death, while it was innocuous in normal mice. An mAb directed against complement receptor type 3 (CR3) was ineffective, as were injections of soluble human ICAM-1. These results suggest that adhesion of LFA-1+ cells to endothelial cells, stimulated by TNF to express high levels of ICAM-1, is critical in the pathogenesis of ECM. Emergency therapy at interfering with cytoadherence could be considered in the treatment of cerebral malaria in man, in which high blood TNF levels are also observed.
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PMID:Late administration of monoclonal antibody to leukocyte function-antigen 1 abrogates incipient murine cerebral malaria. 167 17

Iloprost, a synthetic prostacyclin analog, successfully prevents the development of cerebral malaria in mice. Malaria antigen-induced tumor necrosis factor (TNF) production could be inhibited by iloprost in vitro and in vivo. Northern analysis of TNF mRNA revealed that malaria antigen-induced TNF expression was suppressed at the transcription level.
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PMID:Prevention of murine cerebral malaria by a stable prostacyclin analog. 171 16

Because Plasmodium berghei ANKA induces cerebral malaria and P. vinckei does not, the former has often been studied as a model for human falciparum malaria. It lacks, however, many of the systemic changes seen in the human disease. Because both of these murine models and the human disease have now been defined in terms of excess tumor necrosis factor (TNF) production, the authors have more closely examined the two murine models in this light to see which provides the better overall model for falciparum malaria. Administering TNF to malaria-infected mice did not cause cerebral symptoms nor breakdown of the blood-brain barrier, which is the hallmark of P. berghei ANKA cerebral malaria and is generally absent in human cerebral malaria. Tumor necrosis factor did, however, induce hypoglycemia and liver injury, pathology that is seen in terminal P. vinckei and falciparum malaria, but is absent in terminal P. berghei ANKA malaria. Plasma TNF and interleukin-6 (IL-6) also were found to be consistently higher in infections caused by P. vinckei than in those caused by P. berghei ANKA. The pathology of P. vinckei malaria is thus consistent with raised systemic levels of TNF and other cytokines, as is falciparum malaria. The authors therefore conclude that P. vinckei malaria, although lacking a cerebral component, is the better model for the human disease.
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PMID:Malaria mimicry with tumor necrosis factor. Contrasts between species of murine malaria and Plasmodium falciparum. 173 26

Pentoxifylline, a widely used methylxanthine, was tested for its capacity to prevent cerebral malaria (CM) in Plasmodium berghei ANKA-infected CBA/Ca mice. Nine of 12 control mice developed neurologic signs and died from CM approximately 2 weeks after infection. All 12 mice treated with daily intraperitoneal pentoxifylline (1 mg) for 10 days after infection did not develop CM. All surviving mice developed high parasitemia and severe anemia and died 2 weeks later without neurologic signs. In pentoxifylline-treated mice, serum tumor necrosis factor (TNF) bioactivity was nondetectable, whereas control mice had high TNF levels on day 6 after infection. These findings were supported by in vitro investigations of malaria antigen-induced TNF synthesis. Northern blot analysis of TNF mRNA from stimulated macrophages showed that pentoxifylline inhibited TNF expression at the transcription level, and TNF bioactivity in supernatants was strongly depressed. These findings make pentoxifylline a potential candidate for study as a supportive agent in human CM.
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PMID:Pentoxifylline prevents murine cerebral malaria. 186 48

We examined the capacity of murine recombinant tumor necrosis factor (rmTNF) to induce an inhibitory effect at the hepatic stage on malaria induced by Plasmodium yoelii sporozoites. When injected three times, 1.0 micrograms of rmTNF was found to protect 78% of mice against a sporozoite challenge. In contrast, whatever the dose and the schedule of administration, no inhibition was observed when purified hepatocyte cultures were infected with P. yoelii. The addition of non-parenchymal hepatic cells to hepatocyte cultures restored the capacity of TNF to modulate hepatic stage development, leading to up to 44% inhibition. Antibodies to interleukin 6 reversed the anti-parasite activity in the co-culture system.
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PMID:TNF inhibits malaria hepatic stages in vitro via synthesis of IL-6. 187 39

Malaria infection crisis, at which the parasitemia drops precipitously and the parasite loses infectivity to the mosquito vector, occurs in many natural malaria systems, and has not been explained. We demonstrate that in a simian malaria parasite (Plasmodium cynomolgi in its natural host, the toque monkey), the loss of infectivity during crisis is due to the death of circulating intraerythrocytic gametocytes mediated by crisis serum. These parasite-killing effects in crisis serum are due to the presence in the serum of cytokines tumor necrosis factor and interferon gamma, which are produced by the host as a result of the malaria infection. The killing activity of each cytokine is absolutely dependent upon the presence of additional, as yet unidentified factor(s) in the crisis serum.
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PMID:Cytokines kill malaria parasites during infection crisis: extracellular complementary factors are essential. 190 73

The plasma levels of tumor necrosis factor were measured during a longitudinal survey of 84 subjects living in an endemic area of malaria. In most cases, the plasma tumor necrosis factor was found at its highest level during the malaria transmission peak and became normal again during the dry season. Children having suffered from malarial attack keep low tumor necrosis factor levels compared to adults and asymptomatic children. These results suggest that tumor necrosis factor could be associated with the development of resistance against malaria.
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PMID:Plasma levels of tumor necrosis factor during a longitudinal survey in an endemic area of malaria. 196 8


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