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

To investigate the relation of tumor necrosis factor-alpha (TNF alpha) to Plasmodium falciparum infection, plasma TNF alpha concentrations were measured in Zairian children with severe malaria, mild malaria, or other illnesses. The initial geometric mean plasma concentration of TNF alpha among 61 children with P. falciparum infection, (71 pg/ml) was higher than the level in 26 severely ill, aparasitemic children (10 pg/ml; P less than .001). Among 29 parasitemic children, initial geometric mean TNF alpha levels decreased from 77 to 5 pg/ml (P less than .001) at day 7. TNF alpha levels increased with parasite density and were associated with hyperparasitemia, severe anemia, hypoglycemia, and young age but not with cerebral malaria or fatal outcome. However, TNF alpha levels were elevated equally in children with cerebral malaria and with other signs of severe malaria. With multiple linear regression, TNF alpha levels were elevated independently in children with hyperparasitemia (P = .001) and severe anemia (P = .04). In this study, high TNF alpha levels were associated with several manifestations of severe malaria and were not specific to cerebral malaria.
 ...
PMID:Tumor necrosis factor and severe malaria. 198 82

There is growing evidence that cytokines (interleukin [IL] 1, IL 6, interferon-gamma, tumor necrosis factor [TNF]) directly or indirectly interfere with the intrahepatic development of malaria parasites. Recent work in our laboratory clearly showed that TNF can affect the hepatic development of parasites via IL 6 secreted by liver nonparenchymal cells. The possible participation of an L-arginine-dependent effector mechanism has been studied to explain the TNF/IL 6-induced inhibition. We thus investigated if NGmonomethyl-L-arginine and N omega-nitro-L-arginine, two specific inhibitors of inorganic nitrogen oxide synthesis from L-arginine, were able to affect the inhibitory effect of TNF and/or IL 6 in co-cultures. At 0.1 and 0.5 mM both L-arginine analogues reversed the inhibitory effect of these cytokines. An interesting observation is that L-arginine analogues enhance schizont development in the absence of prior cytokine contact. This result indicates an hepatic basal L-arginine-dependent anti-parasitic activity which might explain the existence of self-degenerating hepatic forms as previously reported.
 ...
PMID:L-arginine-dependent destruction of intrahepatic malaria parasites in response to tumor necrosis factor and/or interleukin 6 stimulation. 199 87

To determine whether isolates of Plasmodium falciparum have intrinsically different cytoadherent properties and whether these differences contribute to the clinical severity of human falciparum malaria, we studied the cytoadherence to C32 melanoma cells in vitro of 59 parasite isolates from patients with naturally acquired infections in Thailand. Parasitized erythrocytes adhere to these melanoma cells principally via the glycoprotein CD36, which is also expressed on most vascular endothelium. In vitro cytoadherence was significantly greater for isolates from patients with biochemical evidence of severe malaria. The cytoadherent properties of P. falciparum parasites may thus be a virulence factor in human falciparum malaria. However, there was no correlation between the degree of in vitro cytoadherence and cerebral symptoms, which suggests that other receptors and/or host factors may be important in the adherence of malaria parasites to cerebral vascular endothelium. The cytokines tumor necrosis factor, interleukin-1, and gamma interferon, which have been implicated in the pathogenesis of cerebral malaria and are known to promote intercellular adhesion in other systems, did not enhance the cytoadherence of P. falciparum isolates to C32 melanoma cells.
 ...
PMID:Clinical correlates of in vitro Plasmodium falciparum cytoadherence. 199 37

The production of Interleukin 6 (IL-6) was studied during experimental cerebral malaria (ECM) induced by Plasmodium berghei ANKA (PbA) infection. IL-6 is present in the serum of mice with ECM, the highest concentrations being observed in mice with full-blown neurological syndrome. High IL-6 levels were also observed, however, in the absence of pathology in nonlethal malaria infection. These data suggest that IL-6 is produced in large amounts during malaria infection, but does not play a major role in the pathogenesis of ECM. A modulation of IL-6 production in ECM was achieved by in vivo treatment with other anticytokine antibodies: antibodies to interferon (IFN-gamma) or to tumor necrosis factor (TNF) abolished the rise of IL-6, while anti-IL-3 and anti-granulocyte/macrophage colony-stimulating factor antibodies only partially prevented this rise, suggesting that the two cytokines IFN-gamma and TNF are important intermediates in IL-6 production. Passive immunization against IL-6 did not prevent ECM, but significantly reduced serum IgG levels in malaria-infected mice. Thus, by its effects on B cells, IL-6 may be involved in hypergammaglobulinemia and immune-complex diseases, e.g., glomerulonephritis observed during malaria infection.
 ...
PMID:Interleukin 6 production in experimental cerebral malaria: modulation by anticytokine antibodies and possible role in hypergammaglobulinemia. 212 90

There is now significant evidence that tumor necrosis factor (TNF) is involved in the pathogenesis of malaria. We have tested sera from patients presenting with a febrile illness admitted to hospital in Honiara, Solomon Islands, for the presence of TNF, interferon-gamma, and interleukin-1 (IL-1). This study differs from previous reports as the subjects were mainly adults from a semi-immune population living in an endemic area. The results from 2 different commercially-available assays for TNF were compared, and one was found to be superior to the other. Serum TNF concentrations correlated with malarial parasite density and the patients' temperatures, but not with interferon or IL-1. The results are discussed in the context of the immunopathology of this disease.
 ...
PMID:Serum tumor necrosis factor associated with malaria in patients in the Solomon Islands. 212 52

The contribution of the T cell- and macrophage-derived cytokines, interferon-gamma (IFN-gamma) and tumor necrosis factor (TNF), respectively, in the cell-mediated mechanisms leading to acquired immunity to blood-stage Plasmodium chabaudi AS was investigated. To examine the contribution of IFN-gamma, resistant C57BL-derived mice were treated during infection with two different neutralizing, anti-murine IFN-gamma mAbs. Such treatment impaired the ability of the host to limit parasite multiplication just before and at the time of the peak parasitemia but did not abrogate the development of acquired immunity resulting in control and elimination of acute infection. The requirement of endogenous IFN-gamma around the time of the peak parasitemia was confirmed by quantification of IFN-gamma production in vitro by spleen cells from infected animals in response to malaria antigen. To investigate the role of TNF, resistant C57BL/6 and susceptible A/J mice were treated with rTNF during P. chabaudi AS infection. Treatment with 10(3) or 10(5) U rTNF resulted in increased resistance in A/J hosts (that is, increased survival and a less severe course of infection); there was no difference between control and treated C57BL/6 mice in the course of infection but there was increased mortality among the animals treated with rTNF. Splenic macrophages harvested from C57BL/6 mice during infection were found to produce high levels of TNF from day 3 to day 28 post-infection. In conclusion, both IFN-gamma and TNF appear to contribute to host resistance to blood-stage infection with P. chabaudi AS.
 ...
PMID:Role of interferon-gamma and tumor necrosis factor in host resistance to Plasmodium chabaudi AS. 212 23

A 38-year-old patient with cerebral P. falciparum malaria was admitted 12 days after a short trip to Kenya. The serum level of tumor necrosis factor (TNF-alpha) was elevated (251 pg/ml). In contrast, Protein C (plasma activity 36.1%; antigen concentration 31.7%) and protein C inhibitor 1 (activity 0.55 U/ml) levels were decreased. This suggested a state of functional activation of the clotting system which was confirmed by elevated levels (4.8 ng/ml) of circulating thrombin-antithrombin-III-complexes (TAT). Protein S (total and free) and coagulation factor IX levels were within normal range. Under successful antiparasitic therapy, TNF-alpha as well as protein C and protein C inhibitor 1 levels returned to baseline within one week. In the context of other studies that demonstrate procoagulant effects of TNF-alpha, it is remarkable that in the case of complicated P. falciparum malaria, an elevated concentration of TNF-alpha can be paralleled by a decreased plasma level of protein C and an increase in TAT suggesting a procoagulant state.
 ...
PMID:[Malaria tropica with activation of blood coagulation and detection of tumor necrosis factor (NF-alpha) in serum]. 215 19

The production of cytokines such as tumor necrosis factor (TNF) may contribute to the pathology of malaria. We showed previously that crude preparations of heat-stable exoantigens from parasite cultures induce the release of TNF in vitro and in vivo. When separated from the culture medium by affinity chromatography, in which immune immunoglobulin G was used as ligand, the mixture of exoantigens of Plasmodium falciparum retained the capacity to induce the secretion of TNF, both by human monocytes from Gambian children and by mouse macrophages. Two individual antigens, Ag1 and Ag7, further purified by affinity chromatography and identified by crossed immunoelectrophoresis, also stimulated TNF production by both types of cell but differed in other functional properties. Thus, the activity of Ag7, but not that of Ag1, was inhibited by polymyxin B, and antisera made against boiled exoantigens of the rodent parasite Plasmodium yoelii which blocked the ability of these antigens to induce the production of TNF also inhibited the activity of Ag7 without affecting Ag1. Since the prevalence of antibody against Ag7 in sera from children in endemic areas appears to correlate with the development of immunity against the manifestations of the disease, this antigen may be one cause of pathology, perhaps through its ability to induce the production of TNF. Its serological relationship with rodent exoantigens suggests that it might be a candidate for an anti-disease vaccine which has the advantage that its active moiety is not subject to significant antigen polymorphism.
 ...
PMID:Two soluble antigens of Plasmodium falciparum induce tumor necrosis factor release from macrophages. 220 38

In cerebral malaria, pathological changes can be found in the brain of infected people and in the brain of Plasmodium berghei-infected mice. The pathogenesis of cerebral malaria in mice is believed to be due to an immunopathological reaction giving rise to an excessive production of cytokines such as interferon gamma (IFN-gamma) and tumor necrosis factor (TNF). We find that low doses of interleukin 1 (IL-1) protect mice against cerebral malaria; IL-1 also inhibits parasitemia. The IL-1 effect on parasitemia was not observed in nude mice and was at least partly reversed in mice treated with IL-1 in combination with antibody to IFN-gamma, indicating the involvement of T cells. Mice protected against development of cerebral malaria by IL-1 treatment developed the syndrome when TNF was given as observed in control infected mice or infected mice treated with inactivated IL-1.
 ...
PMID:Low dosages of interleukin 1 protect mice against lethal cerebral malaria. 223 Jun 43

Experimental cerebral malaria (ECM), a lethal hyperacute neurological syndrome associated with high blood levels of tumor necrosis factor, develops in genetically susceptible (CBA/Ca) mice 7 days after infection with Plasmodium berghei ANKA strain. Injections of neutralizing monoclonal antibody against recombinant murine interferon gamma, not later than 4 days after infection, markedly reduced the incidence of ECM and the elevation in serum levels of tumor necrosis factor. This treatment prevented the cerebral lesions (plugging of brain vessels by monocytes, lymphocytes, and parasitized erythrocytes). In contrast, the extent of macrophage infiltration in lymphoid organs (which is a characteristic feature of mice developing ECM), as well as the course of infection, remained unaffected by the antibody treatment. Protected mice died at a later time of severe anemia and overwhelming parasitemia, the usual outcome of P. berghei infection in mice that are not susceptible to ECM. The present data indicate that interferon gamma constitutes an important link in the cytokine network that leads to brain vessel inflammation in experimental malaria. It is proposed that interferon gamma released by activated CD4+ T cells acts by augmenting both production and action of tumor necrosis factor.
 ...
PMID:Monoclonal antibody against interferon gamma can prevent experimental cerebral malaria and its associated overproduction of tumor necrosis factor. 250 93


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>