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)

Cytokine unbalance is responsible for the pathogenesis of diverse inflammatory, autoimmune and infectious diseases, and Tumor Necrosis Factor Alpha (TNF alpha), among other cytokines, plays a central role. TNF alpha production can be regulated at the transcriptional, post-transcriptional, and translational levels. Variability in the promoter and coding regions of the TNF alpha gene may modulate the magnitude of its secretory response. Up to date, several single nucleotide polymorphisms (SNPs) have been identified in the human TNF alpha gene promoter. One of these, is a guanine to adenine transition at position -308, that generates the TNF1 and TNF2 alleles, respectively. The TNF2 allele is associated to a high in vitro TNF expression, and it has also been linked to an increased susceptibility and severity, for a variety of illnesses, such as rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, Alzheimer disease and cerebral malaria among others. It is also associated with a higher septic shock susceptibility and mortality. The investigation of polymorphisms within the TNF alpha cluster will be important in understanding the role of TNF alpha regulation in specific diseases.
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PMID:[Tumor necrosis factor alpha genetic polymorphism as a risk factor in disease]. 1243 54

Physiologically in the brain, cytokines such as tumor necrosis factor-alpha (TNalpha) are released by the immune system and can modulate neurological responses. Conversely, the central nervous system (CNS) is also able to modulate cytokine production. In the case of CNS disorders, cytokine release may be modified. Cerebral malaria (CM) is a complication of Plasmodium falciparum infection in humans and is characterized by a reversible encephalopathy with seizures and loss of consciousness. Central clinical signs are partly due to sequestration of parasitized red blood cells in the brain microvasculature due to interactions between parasite proteins and adhesion molecules. TNFalpha is produced and released by host cells following exposure to various malarial antigens. The increase of TNFalpha release is responsible for the overexpression of adhesion molecules. This article reviews the involvement of TNFalpha in cerebral malaria and the relation with all the processes involved in this pathology. It shows that (i). TNFalpha levels are increased in plasma and brain but with no clear correlation between TNFalpha levels and occurrence and severity of CM; (ii). TNFalpha is responsible for intercellular adhesion molecule-1 upregulation in CM, the relation being less clear for other adhesion molecules; (iii). TNFalpha receptors are upregulated in CM, with TNF receptor 2 (TNFR2) showing a higher upregulation than TNFR1 in vivo; (iv). in murine CM, low doses of TNFalpha seem to protect from CM, whereas excess TNFalpha induces CM and anti-TNFalpha therapies (antibodies, pentoxifylline) did not show any efficiency in protection from CM. Moreover, the involvement of lymphotoxin a, which shares with TNFalpha the same receptors with similar affinity, appears to be an interesting target for further investigation.
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PMID:Tumor necrosis factor alpha in the pathogenesis of cerebral malaria. 1450 53

The pro-inflammatory cytokine tumour necrosis factor alpha (TNF-alpha) is associated with malaria virulence (disease severity) in both rodents and humans. We are interested in whether parasite genetic diversity influences TNF-mediated effects on malaria virulence. Here, primary infections with genetically distinct Plasmodium chabaudi chabaudi (P.c.c.) clones varied in the virulence and cytokine responses induced in female C57BL/6 mice. Even when parasitaemia was controlled for, a greater day 7 TNF-alpha response was induced by infection with more virulent P.c.c. clones. Since many functions of TNF-alpha are exerted through TNF receptor 1 (TNFR1), a TNFR-1 fusion protein (TNFR-Ig) was used to investigate whether TNFR1 blockade eliminated clone virulence differences. We found that TNFR-1 blockade ameliorated the weight loss but not the anaemia induced by malaria infection, regardless of P.c.c. clone. We show that distinct P.c.c. infections induced significantly different plasma interferon gamma (IFN-gamma), interleukin 6 (IL-6) and interleukin 10 (IL-10) levels. Our results demonstrate that regardless of P.c.c. genotype, blocking TNFR1 signalling protected against weight loss, but had negligible effects on both anaemia and asexual parasite kinetics. Thus, during P.c.c. infection, TNF-alpha is a key mediator of weight loss, independent of parasite load and across parasite genotypes.
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PMID:Parasite genetic diversity does not influence TNF-mediated effects on the virulence of primary rodent malaria infections. 1697 51

The hypothesis that tumor necrosis factor (TNF) aggravates malaria in children is supported by observations that TNF polymorphisms and high TNF levels have been associated with cerebral malaria. Nevertheless, severe malaria was not associated with polymorphisms located at positions -308A and -238A in the TNF alpha gene promoter or with a high TNF level in plasma in children from Bamako, Mali.
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PMID:Alleles 308A and 238A in the tumor necrosis factor alpha gene promoter do not increase the risk of severe malaria in children with Plasmodium falciparum infection in Mali. 1698 33

Severe malaria is associated with sequestration of Plasmodium falciparum-infected red blood cells (PRBC) in the microvasculature and elevation of intercellular adhesion molecule-1 (ICAM-1) and TNF. In vitro co-culture of human umbilical vein endothelial cells (HUVEC), with either PRBC or uninfected RBC, required the presence of low level TNF (5pg/ml) for significant up-regulation of ICAM-1, which may contribute to increased cytoadhesion in vivo. These effects were independent of P. falciparum erythrocyte membrane protein-1 (PfEMP-1)-mediated adhesion but critically dependent on cell-cell contact. Further changes included increases in IL8 release and soluble TNF receptor shedding. Microarray analysis of HUVEC transcriptome following co-culture, using a human Affymetrix microarray chip, showed significant differential regulation of genes which defined gene ontologies such as cell communication, cell adhesion, signal transduction and immune response. Our data demonstrate that endothelial cells have the ability to mobilise immune and pro-adhesive responses when exposed to both PRBC and TNF. In addition, there is also a previously un-described positive regulation by RBC and TNF and a concurrent negative regulation of a range of genes involved in inflammation and cell-death, by PRBC and TNF. We propose that the balance between positive and negative regulation demonstrated in our study will determine endothelial pathology during a malaria infection.
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PMID:Altered phenotype and gene transcription in endothelial cells, induced by Plasmodium falciparum-infected red blood cells: pathogenic or protective? 1738 56

Reducing host carriage of transmission-stage malaria parasites (gametocytes) is expected to decrease the population-wide burden of malaria. Some malaria disease severity is attributed to the induction of the pro-inflammatory cytokines TNF-alpha and lymphotoxin-alpha (LT-alpha), and we are interested in whether anti-malaria interventions which ameliorate the symptoms induced by those cytokines may have the capacity to alter malaria transmission. As many functions of TNF-alpha and LT-alpha are exerted through TNF receptor 1 (TNFR1), we investigated the effect TNFR1 blockade exerted on parasite transmission using the rodent malaria Plasmodium chabaudi chabaudi. We found that blocking TNFR1 simultaneously increased gametocyte density and infectivity to mosquitoes, whilst reducing disease severity (weight loss). These transmission-enhancing and severity-reducing effects of TNFR1 blockade were independent of asexual parasite load and were observed for several P. c. chabaudi genotypes. These results suggest that the effects of candidate malaria interventions on infectivity should be examined alongside effects on disease severity so that the epidemiological consequences of such interventions can be evaluated.
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PMID:Blockade of TNF receptor 1 reduces disease severity but increases parasite transmission during Plasmodium chabaudi chabaudi infection. 1822 16

Periodic fever syndromes are a group of diseases characterized by episodes of fever with healthy intervals between febrile episodes. The first manifestation of these disorders are present in childhood and adolescence, but infrequently it may be presented in young and middle ages. Genetic base has been known for all types of periodic fever syndromes except periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA). Common periodic fever disorders are Familial Mediterranean fever (FMF) and PFAPA. In each patient with periodic fever, acquired infection with chronic and periodic nature should be ruled out. It depends on epidemiology of infectious diseases. Some of them such as Familial Mediterranean fever and PFAPA are common in Iran. In Iran and other Middle East countries, brucellosis, malaria and infectious mononucleosis should be considered in differential diagnosis of periodic fever disorders especially with fever and arthritis manifestation. In children, urinary tract infection may be presented as periodic disorder, urine analysis and culture is necessary in each child with periodic symptoms. Some malignancies such as leukemia and tumoral lesions should be excluded in patients with periodic syndrome and weight loss in any age. After excluding infection, malignancy and cyclic neutropenia, FMF and PFAPA are the most common periodic fever disorders. Similar to other countries, Hyper IgD, Chronic Infantile Neurologic Cutaneous and Articular, TRAPS and other auto-inflammatory syndromes are rare causes of periodic fever in Iranian system registry. In part 1 of this paper we reviewed the prevalence of FMF and PFAPA in Iran. In part 2, some uncommon auto-inflammatory disorders such as TRAPS, Hyper IgD sydrome and cryopyrin associated periodic syndromes will be reviewed.
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PMID:Periodic Fever: a review on clinical, management and guideline for Iranian patients - part I. 2579 39


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