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

Cerebral malaria is a life threatening sequel of Plasmodium falciparum infection and contributes significantly to malaria mortality, especially among children. Accumulation of macrophages and proliferation of microglial cells play key roles in cerebral malaria and are thought to contribute to the pathophysiological alterations observed in these patients, which include enhanced adherence of infected erythrocytes to the cerebral vasculature by expression and secretion of proinflammatory molecules, disruption of the blood-brain barrier, recruitment of other inflammatory cells to the lesion site. In this review, recent advances in the understanding of the involvement of macrophages/microglial cells in the development of cerebral malaria are summarized.
Eur Cytokine Netw
PMID:Macrophages/microglial cells in patients with cerebral malaria. 1210 Oct 73

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

Human immunodeficiency virus (HIV) infection is the primary cause of morbidity and mortality in Malawi, Africa, because of its many effects on the immune system. Immune cells communicate through cytokines; therefore, we examined the relationships between HIV serostatus and cell-specific cytokine production for 40 asymptomatic, employed adults and 312 acutely ill, hospitalized patients in Malawi. We also measured the plasma HIV-1 RNA levels of 13 asymptomatic persons and 83 patients found to be HIV(+). We incubated peripheral whole blood with brefeldin-A +/- phorbol 12-myristate 13-acetate and ionomycin and then permeabilized, fixed, fluorescently stained, and examined the mononuclear cells with four-color, six-parameter flow cytometry. The percentage of lymphocytes expressing CD4 did not differ significantly between the HIV(+) and HIV(-) healthy adults (medians, 35.2 vs. 40.8%, respectively), but a wide array of cytokine parameters were lower in the HIV(+) than in the HIV(-) asymptomatic persons, for example, median percentages of T cells producing induced interleukin 2 (IL-2) (8.7 vs. 16.5%, respectively) and spontaneously producing IL-6 (0.7 vs. 11.0%, respectively). Also, four T cell parameters reflecting type 2-to-type 1 cytokine balances (T2/T1) were higher in the HIV(+), versus HIV(-), asymptomatic persons. Unlike the healthy adults, for patients with mycobacteremia/fungemia or malaria, the HIV(+) patients had higher median percentages of T cells and CD8(+) T cells producing induced interferon gamma than did the HIV(-) PATIENTS: For both asymptomatic and acutely ill persons, HIV-1 plasma levels were positively correlated with T2/T1 parameters. Cell-specific cytokine effects of HIV infection may precede measurable effects on CD4 expression. Cytokine therapies, even beyond periodic administration of IL-2, may improve the responses of HIV-infected persons to both HIV and coinfections.
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PMID:Peripheral blood cell-specific cytokines in persons with untreated HIV infection in Malawi, Africa. 1248 8

The interaction between pro- and anti-inflammatory cytokines such as interleukin 12 (IL-12), interleukin 18 (IL-18) and transforming growth factor beta (TGF-beta) may play an important role in malaria pathogenesis and outcome. IL-18 cooperates with IL-12 in the IFN-gamma production by T, B, and NK cells, and synergizes with IL-12 for IFN-gamma production by Th1 cells. Recently it has been demonstrated that these cytokines modulate the immunoresponse in Plasmodium falciparum malaria. The aim of this study was to measure the plasma levels of IL-12, IL-18 and TGF-beta in 105 African children with various degrees of malaria, and correlate the production of these cytokines with the severity of the disease. IL-12, IL-18 and TGF-beta levels were determined using enzyme-linked immunosorbent assay. The severity of malaria was established by parasitemia, clinical symptoms and haematological parameters. The levels of IL-12, IL-18 and TGF-beta were found to be significantly elevated (15.6 + / - 12.3, 22.7 + / - 13.8 pg/ml and 25.14 + / - 13.22 pg/ml respectively) in all of the children. IL-12 and IL-18 levels were significantly lower (13.2 + / - 5.53 and 21.5 + / - 10 pg/ml pg/ml) in children with severe disease, whereas the level of TGF-beta was higher (28.09 + / - 12.39 pg/ml). In contrast, IL-12 and IL-18 levels were found to be higher (17.32 + / - 7.8 pg/ml and 25.7 + / - 7.6 pg/ml) in patients with mild disease, whereas the level of TGF-beta was lower (20.92 + / - 12.76 pg/ml) compared to the severe malaria group. The correlation between IL-12 and IL-18 demonstrated a progressive relationship up to a value of IL-12 < 25 pg/ml, while IL-18 remained stable at higher levels of IL-12. An inverse correlation was found between IL-12 and TGF-beta up to a value of IL-12 < 30, after which the level of TGF-beta remained stable. This finding suggests that fine mechanisms regulate the interaction between IL-12, IL-18 and TGF-beta in the immune response to Plasmodium falciparum.
Eur Cytokine Netw
PMID:Plasma levels of interleukin-12 (IL-12), interleukin-18 (IL-18) and transforming growth factor beta (TGF-beta) in Plasmodium falciparum malaria. 1688 79

Aiming to clarify the role of endogenous interleukin-12 (IL-12) in protective immunity against blood stages of Plasmodium chabaudi chabaudi (AS), we evaluated the course of infection in IL-12p40 gene knockout (IL-12p40KO) and wild-type (WT) C57BL/6 mice, focusing (1) on the ability of T cells to develop adequate type 1 responses and (2) on the potentiality of macrophages to respond to parasites, interferon-gamma (IFN-gamma), or both. We observed that IL-12p40KO mice develop significantly higher parasitemias during the acute infection, although mice from both groups clear the parasites within a month and similarly eliminate a secondary challenge. Thus, fully protective immunity to P. c. chabaudi can be generated in the absence of IL-12. However, this cytokine may promote parasite control during the early phase of infection. The increased acute parasitemia of IL-12p40KO mice was associated with both impaired IFN-gamma and nitric oxide (NO) response by spleen cells. Because stimulation with recombinant IFN-gamma (rIFN-gamma) failed to improve the NO response in IL-12p40KO macrophages, we investigated whether these cells have an intrinsic defect. Analysis of peritoneal macrophages revealed that IL-12p40KO cells produce higher levels of transforming growth factor-beta1 (TGF-beta1) compared with WT cells and respond to infected erythrocytes or rIFN-gamma by releasing little NO. Moreover, IL-12p40KO macrophages had a severely impaired ability to internalize opsonized infected erythrocytes, suggesting that the low effector profile assumed by these cells may compromise antibody-mediated immunity. Taken together, our results support the idea that the absence of IL-12p40 not only affects IFN-gamma production but also has deep consequences in macrophage effector functions that may contribute to exacerbation of the early phase of P. c. chabaudi malaria.
J Interferon Cytokine Res 2002 Dec
PMID:Impaired macrophage responses may contribute to exacerbation of blood-stage Plasmodium chabaudi chabaudi malaria in interleukin-12-deficient mice. 1258 92

The interaction between pro- and anti-inflammatory cytokines such as interleukin 12 (IL-12), interleukin 18 (IL-18) and transforming growth factor beta (TGF-beta) plays an important role in malaria pathogenesis and outcome, modulating the immunoresponse in Plasmodium falciparum malaria. In our previous studies, we analyzed the plasmatic levels of IL-12, IL-18 and TGF-beta in 105 African children with different degrees of malaria and we correlated the production of these cytokines with the severity of the disease. The aim of the present study was to analyze with a mathematical model, taking into account all the relationships between these cytokines and the parameter variations involved in malaria pathogenesis that influence the results of each type of treatment or therapeutic protocol on patients at different stages of the disease. A mathematical correlation was demonstrated between the levels of pro-inflammatory and anti-inflammatory cytokines, and from this it was possible to build curves of reference in which each patient was positioned based on IL-12 level. Our data, obtained in patients with mild and severe diseases, demonstrate that the levels of IL-12 represent a reliable parameter to predict the progression of the disease, which may be complemented or modulated by administration of IL-18 and TGF-beta. Our findings provide future implications for an immune therapy against the P. falciparum malaria infection, especially in the early phase of the disease showing that a more aggressive outcome may be due to the lack of a balanced immune response.
Cytokine 2003 Feb 21
PMID:Modulation of immune response in Plasmodium falciparum malaria: role of IL-12, IL-18 and TGF-beta. 1688 79

Studies of naturally-acquired immunity to malaria in endemic regions provide the potential for a greater understanding of the regulation of human immune responses to the malarial parasite. However, little is known about the acquisition of malaria-specific immunity in regions of unstable, meso-endemic or hypo-endemic transmission. Cytokine profiles - patterns in the expression of interleukin-4 (IL-4), interleukin-10, interleukin-12, interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) - were therefore studied during the natural acquisition of immunity to Plasmodium falciparum and P. vivax among individuals from Buenaventura, a meso-endemic region on the Pacific Coast of Colombia. In general, specific type-1 immune responses, characterized by IFN-gamma expression, were more likely to develop during P. falciparum infection, whereas pro-inflammatory cytokine profiles (with TNF-alpha expression) were observed more frequently among the P. vivax infections. Type-2 cytokine profiles, characterized by dominant IL-4 expression, were infrequent. Expression of IL-4 probably occurs primarily after prolonged exposure to parasites (which would, by definition, not be common in a meso-endemic region).
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PMID:Human cytokine responses to meso-endemic malaria on the Pacific Coast of Colombia. 1283 18

The ability of human NK cells to inhibit the growth in vitro of the asexual blood stages of Plasmodium falciparum was tested. Purified NK cells from donors with no prior exposure to malaria significantly inhibited parasite growth after 48 hours of co-culture in the presence of human immune serum. This inhibition was completely abrogated by pre-treatment of the NK cells with an anti-CD95 (anti-Fas) monoclonal antibody and human Fas-Fc soluble protein. The level of growth inhibition was also substantially reduced by pre-treatment with an anti-CD56 antibody. These two antibodies caused reductions, to varying levels, of the amounts of NK cell-derived granzyme B (GrB) and pro-inflammatory cytokines, but only the anti-CD95 antibody affected the production of soluble Fas ligand (sFasL). Direct destruction of parasite-infected red cells by NK cells, in the absence of serum, was also observed in a standard 51Cr cytotoxicity test, during which N-carboxybenzoxy-L-lysine thiobenzil ester (BLT esterase) activity, which catalyzes serine protease granule release, was detected. The results obtained are indicative of a novel mechanism of NK cell-mediated cytotoxic activity against Plasmodium falciparum-infected red cells, which is mediated in part by both Fas and by GrB.
Eur Cytokine Netw
PMID:Natural killer (NK) cell-mediated cytolysis of Plasmodium falciparum-infected human red blood cells in vitro. 1465 86

To investigate if severe malarial anemia is associated with specific cytokine overproduction, we evaluated serum levels of soluble Fas ligand (sFasL), tumor necrosis factor (TNF-alpha) and interleukin-10 (IL-10) from three groups of young children with Plasmodium falciparum infection (asymptomatic cases, uncomplicated malaria cases and severe malarial anemia cases), in a hyperendemic area of Gabon. In uncomplicated cases, only TNF levels were significantly (p < 0.001) increased in comparison to asymptomatic cases with P. falciparum infection. High levels of sFasL, TNF-alpha and IL-10 were associated with low hemoglobin concentrations, sFasL levels were significantly higher in children with severe malarial anemia (p < 0.001) as compared to both other groups. The parasite density was positively correlated with IL-10, TNF-alpha and sFasL levels. TNF-alpha and sFasL, but not IL-10 or parasitemia, were independent predictors of hemoglobin concentrations. These results suggest that, in malaria, a specific dysregulation of the cytokine balance may lead to complications such as severe anemia.
Eur Cytokine Netw
PMID:Severe malarial anemia associated with increased soluble Fas ligand (sFasL) concentrations in Gabonese children. 1471 16

The G to A single nucleotide polymorphisms (SNPs), at position -376, -308 and -238 in the promoter of the tumor necrosis factor alpha (TNF) gene, have been independently correlated with numerous diseases. Alleles TNF(-376A) and TNF(-238A) are normally found throughout the world with very low frequencies. We investigated the frequency of these SNPs in Sicilian subjects hospitalized after traumatic brain injury and in three groups of subjects from northern Sardinia: healthy subjects and individuals with multiple sclerosis or ischemic stroke. While no significant difference was found between healthy and disease subjects, the frequency of TNF(-376A) and TNF(-238A) was elevated up to 10 times in Sardinia compared to Sicily and other populations throughout the world. These elevated frequencies may be the result of genetic drift or of selective pressure on TNF itself or on neighboring genes, including the HLA. Malaria, endemic to Sardinia until the end of the 1940s, and the bubonic plague, are among the possible causes of selection. These findings indicate that Sardinia is an ideal location to further elucidate the correlation between TNF or HLA polymorphisms and diseases, including multiple sclerosis and type-I diabetes, present with an unusually high frequency and co-morbidity in Sardinia.
Cytokine 2004 May 21
PMID:High frequency of TNF alleles -238A and -376A in individuals from northern Sardinia. 1514 31


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