Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasmodium berghei ANKA causes lethal malaria in mice. It is well established that C57BL/6 mice die early with fulminant symptoms including convulsion, whereas BALB/c mice survive this phase and die later of anemia and prostration. Early death in C57BL/6 mice has been considered to result from the adverse effects of inflammatory cytokines. To elucidate the CD4(+) T cell responses in early death due to severe malaria, the kinetics of CD4(+) T cells were compared by analyzing cell surface markers and the production of cytokines and transcription factors. The results revealed that cytokine production by CD4(+) T cells was induced as early as 5 days after infection and the maintenance of higher levels of IL-4 and IL-10 may be associated with the protection of BALB/c mice from early death. These results suggest that parasite control in the early phase of infection may be important for the development of an effective vaccine.
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PMID:CD4(+) T cell response in early erythrocytic stage malaria: Plasmodium berghei infection in BALB/c and C57BL/6 mice. 1935 3

Regulated upon activation, normal T-cell expressed, and secreted (RANTES, CCL-5) is an important immunoregulatory mediator that is suppressed in children with malarial anemia (MA). Although pro-inflammatory (e.g., TNF-alpha, IL-1beta and IFN-gamma) and anti-inflammatory (e.g., IL-4, IL-10 and IL-13) cytokines regulate RANTES production, their effect on RANTES in children with MA has not been determined. Since intraleukocytic malarial pigment, hemozoin (Hz), causes dysregulation in chemokine and cytokine production, the impact of naturally acquired Hz (pfHz) on RANTES and RANTES-regulatory cytokines (TNF-alpha, IFN-gamma, IL-1beta, IL-4, IL-10, and IL-13) was examined. Circulating RANTES levels progressively declined with increasing levels of pigment-containing monocytes (PCM) (P=0.035). Additional experiments in cultured peripheral blood mononuclear cells (PBMC) showed that monocytic acquisition of pfHz (in vivo) was associated with suppression of RANTES under baseline (P=0.001) and stimulated conditions (P=0.072). Although high PCM levels were associated with decreased circulating IFN-gamma (P=0.003) and IL-10 (P=0.010), multivariate modeling revealed that only PCM (P=0.048, beta=-0.171) and IL-10 (P<0.0001, beta=-0.476) were independently associated with RANTES production. Subsequent in vitro experiments revealed that blockade of endogenous IL-10 significantly increased RANTES production (P=0.028) in PBMC from children with naturally acquired Hz. Results here demonstrate that monocytic acquisition of Hz suppresses RANTES production in children with MA through an IL-10-dependent mechanism.
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PMID:Naturally acquired hemozoin by monocytes promotes suppression of RANTES in children with malarial anemia through an IL-10-dependent mechanism. 1942 95

We have previously shown a reduction in anaemia and wasting malnutrition in infants <3 years old in Pemba Island, Zanzibar, following repeated anthelminthic treatment for the endemic gastrointestinal (GI) nematodes Ascaris lumbricoides, hookworm and Trichuris trichiura. In view of the low intensity of worm infections in this age group, this was unexpected, and it was proposed that immune responses to the worms rather than their direct effects may play a significant role in morbidity in infants and that anthelminthic treatment may alleviate such effects. Therefore, the primary aims of this study were to characterise the immune response to initial/early GI nematode infections in infants and the effects of anthelminthic treatment on such immune responses. The frequency and levels of Th1/Th2 cytokines (IL-5, IL-13, IFN-gamma and IL-10) induced by the worms were evaluated in 666 infants aged 6-24 months using the Whole Blood Assay. Ascaris and hookworm antigens induced predominantly Th2 cytokine responses, and levels of IL-5 and IL-13 were significantly correlated. The frequencies and levels of responses were higher for both Ascaris positive and hookworm positive infants compared with worm negative individuals, but very few infants made Trichuris-specific cytokine responses. Infants treated every 3 months with mebendazole showed a significantly lower prevalence of infection compared with placebo-treated controls at one year following baseline. At follow-up, cytokine responses to Ascaris and hookworm antigens, which remained Th2 biased, were increased compared with baseline but were not significantly affected by treatment. However, blood eosinophil levels, which were elevated in worm-infected children, were significantly lower in treated children. Thus the effect of deworming in this age group on anaemia and wasting malnutrition, which were replicated in this study, could not be explained by modification of cytokine responses but may be related to eosinophil function.
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PMID:Early exposure of infants to GI nematodes induces Th2 dominant immune responses which are unaffected by periodic anthelminthic treatment. 1943 45

Chronic lymphocytic leukemia (CLL) is a malignancy of mature B-lymphocytes that manifests in a variety of clinical courses. The accumulation of CLL-cells is primarily caused by defective apoptosis; however, a higher proliferative capacity has also been found to correlate with poorer prognostic factors. Proliferating CLL-cells are confined to specialized structures called pseudofollicles, which contain CLL-cells, T-lymphocytes, and stromal cells. We established an in vitro model for pseudofollicles to characterize the behavior of CLL-cells in relation to clinical courses with different outcomes. Only CLL-cells from progressive clinical cases were inducible to proliferate by a combination of soluble CD40L/IL-2/IL-10 in co-culture with stromal cells. Proliferating CLL-cells showed a higher and more extensive expression of antigens, which are important in T-B-cell interactions such as CD40, MHC II, and adhesion molecules. IL-4 increased interferon regulatory factor-4 expression and induced a specific immunophenotype, which may imply plasmacytic differentiation. Furthermore, it was shown that co-cultured stromal cells protected CLL-cells from apoptosis. CLL-cells from clinically indolent cases had a far worse survival rate in medium than the cells from poor prognostic cases. Thus, we can assume that not only a different resistance to apoptosis, but also proliferation contributes to the progression of CLL resulting in bone marrow failure with thrombocytopenia and anemia.
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PMID:Different proliferative and survival capacity of CLL-cells in a newly established in vitro model for pseudofollicles. 1965 65

It was proven that compound C displays beneficial effects in models of inflammatory-induced anemia, ischemic stroke, and fibrodysplasia ossificans progressiva. Compound C influence on microglia, playing a major role in neuroinflammation, has not been evaluated yet. The aim of the present study was to determine the effect of compound C on cytokine release, NO, and reactive oxygen species (ROS) production. The rat microglial cultures were obtained by shaking the primary mixed glial cultures. Cytokine and nitrite concentrations were assayed using ELISA kits. ROS were assayed with nitroblue tetrazolium chloride. AMPK activity was assayed using the SAMS peptide. The expression of arginase I, NF-kappaB p65, and hypoxia-inducible factor-1 alpha (HIF-1 alpha) was evaluated using Western blot. Compound C displayed ambivalent effect depending on microglia basal activity. It up-regulated the release of TNF alpha and NO production and increased the expression of arginase I in non-stimulated microglia. However, compound C down-regulated IL-1 beta, IL-6 and TNF alpha release, NO, ROS production, and AMPK activity, diminished NF-kappaB and HIF-1 alpha expression, as well as increased arginase I expression in lipopolysaccharide (LPS)-stimulated microglia. Compound C did not affect iNOS expression and IL-10 and TGF-beta release in non-stimulated and LPS-stimulated microglia. The observed alterations in the release or production of inflammatory mediators may be explained by the changes in NF-kappaB, HIF-1 alpha, and arginase I expression and 3-(4,5-dimethylthazol-2-yl)-2,5-diphenyltetrazolinum bromide values in response to LPS, whereas the basis for the compound C effect on non-stimulated microglia remains to be investigated.
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PMID:Ambivalent effects of compound C (dorsomorphin) on inflammatory response in LPS-stimulated rat primary microglial cultures. 2816 17

The aim of this preliminary study was to investigate the plasma cytokine profiles in a group of patients suffering from Plasmodium vivax malaria during the peak of its transmission season. Plasma samples of 173 P. vivax patients and 34 healthy individuals were analyzed for IFN-gamma, TNF-alpha, IL-10 and IP-10 levels by ELISA. Levels of both pro- and anti-inflammatory cytokines were significantly higher in P. vivax patients compared to controls. Children with P. vivax infection had significantly higher levels of IFN-gamma than adults (P=0.017). Asexual parasitaemia versus TNF-alpha (r=-0.31, P=0.01), IL-10 (r=-0.30, P=0.015) and gametocytaemia versus IFN-gamma (r=-0.26; P=0.034) levels showed significant negative correlation in children compared to adults. The median concentrations of IFN-gamma (P=0.001), IL-10 (P=0.032) and IP-10 (P</=0.05) were higher in children reported with chills and rigors, whereas in adults only IFN-gamma levels was higher (P<0.0001). The median plasma concentrations of IFN- gamma (P=0.02), IL-10 (P<0.0001) and IP-10 (P=0.068) were higher in patients with mild anaemia compared to non-anaemic patients. The results indicated that both pro- and anti-inflammatory cytokine responses are associated with clinical signs of mild anaemia and paroxysm during symptomatic P. vivax malaria in Central India.
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PMID:A preliminary study on pro- and anti-inflammatory cytokine profiles in Plasmodium vivax malaria patients from central zone of India. 1995 46

Polyamines are essential for proliferation of Trypanosoma brucei brucei, and feeding rats polyamine-deficient chow (PDC) decreases their blood polyamine concentrations. Proliferation of T. b. brucei (IL-tat 1.4 strain) (IL) is not restrained within PDC-fed rats. However, symptoms of IL-infected rats such as anemia decrease by PDC feeding. We reported cytokine and nitric oxide (NO) production of T. b. gambiense (Wellcome strain [WS])-infected rats were affected by PDC feeding, and WS proliferation was restrained. Therefore, we investigated whether the change in production of cytokines and NO by PDC feeding affects IL proliferation and decreases symptoms in vivo. In IL-infected PDC-fed rats, NO, interleukin (IL)-12, and tumor necrosis factor-alpha production increased while interferon-gamma and IL-10 decreased compared to normal chow-fed rats. IL proliferation was restrained by NO production when it was co-cultured with spleen cells harvested from uninfected rats. In contrast, IL proliferation in infected rats was not changed by PDC feeding, although NO production was increased. The results suggest that changes in cytokines and NO production in IL-infected rats by PDC feeding have little influence on IL proliferation. However, they may serve to decrease symptoms.
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PMID:Effect of polyamine-deficient chow on Trypanosoma brucei brucei infection in rats. 2004 84

Bovine African trypanosomiasis causes severe economical problems on the African continent and one of the most prominent immunopathological parameters associated with this parasitic infection is anemia. In this report we review the current knowledge of the mechanisms underlying trypanosomiasis-associated anemia. In first instance, the central role of macrophages and particularly their activation state in determining the outcome of the disease (i.e. trypanosusceptibility versus trypanotolerance) will be discussed. In essence, while persistence of classically activated macrophages (M1) contributes to anemia development, switching towards alternatively activated macrophages (M2) alleviates pathology including anemia. Secondly, while parasite-derived glycolipids such as the glycosylphosphatidylinositol (GPI) induce M1, host-derived IL-10 blocks M1-mediated inflammation, promotes M2 development and prevents anemia development. In this context, strategies aimed at inducing the M1 to M2 switch, such as GPI-based treatment, adenoviral delivery of IL-10 and induction of IL-10 producing regulatory T cells will be discussed. Finally, the crucial role of iron-homeostasis in trypanosomiasis-associated anemia development will be documented to stress the analogy with anemia of chronic disease (ACD), hereby providing new insight that might contribute to the treatment of ACD.
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PMID:The central role of macrophages in trypanosomiasis-associated anemia: rationale for therapeutical approaches. 2015 97

In animal trypanosomiasis the severity of infection is reflected by the degree of anemia which resembles anemia of inflammation, involving a skewed iron homeostasis leading to iron accumulation within the reticuloendothelial system. Myeloid cells (M cells) have been implicated in the induction and maintenance of this type of anemia and modulation of M cells through the main trypanosome-derived glycosylphosphatidylinositol (GPI)-anchor could attenuate both anemia and trypano-susceptibility in Trypanosoma brucei-infected mice. Herein the GPI-based treatment, allowing a straightforward comparison between trypanotolerance and susceptibility in T. brucei-infected C57Bl/6 mice, was further adopted to scrutinize mechanisms/pathways underlying trypanosome-elicited anemia. Hereby, the following interlinkable observations were made in GPI-based treated (GBT) T. brucei-infected mice: (i) a reduced inflammatory cytokine production and increased IL-10 production associated with alleviation of anemia and restoration of serum iron levels, (ii) a shift in increased liver expression of iron storage towards iron export genes, (iii) increased erythropoiesis in the bone marrow and extramedullar sites (spleen) probably reflecting a normalized iron homeostasis and availability. Collectively, our results demonstrate that reprogramming macrophages towards an anti-inflammatory state alleviates anemia of inflammation by normalizing iron homeostasis and restoring erythropoiesis.
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PMID:Scrutinizing the mechanisms underlying the induction of anemia of inflammation through GPI-mediated modulation of macrophage activation in a model of African trypanosomiasis. 2019 6

The outcome of malarial anemia is determined by a complex interplay between pro-inflammatory and anti-inflammatory cytokines, its severity associated with accumulation of hemozoin (Hz) in macrophages, elevated IL-10 responses and impaired IL-12 production. Although free heme contributes to malarial anemia by inducing oxidative damage of red blood cells (RBCs) and enhancing their clearance by phagocytes, its impact on IL-12/IL-10 interactions has not been fully characterized. Herein, the effect of hemin (HE) on IL-12 and IL-10 responses was studied in murine bone marrow-derived macrophages (BMDM) and compared with synthetic Hz. Our data reveal that HE induces modest inhibition of IL-12p70 responses to lipopolysaccharide (LPS) whereas Hz significantly impairs IL-12p70 responses to IFNgamma/LPS through down-regulation of IL-12p35 and p40 gene expression. Although reactive oxygen species (ROS) are generated after short-term exposure to HE and Hz, prolonged exposure to these iron protoporphyrins has opposite effects on the cellular redox status, HE being the only compound able to promote persistent ROS production. Accordingly, the inhibitory effect of HE on IL-12p70 seems sustained by redox-dependent induction of IL-10 and is partially controlled by the p38 mitogen-activated protein kinase (MAPK) signalling pathway. Indeed, treatment with n-acetylcysteine (NAC) or with the p38 MAPK inhibitor SB203580 inhibits IL-10 responses and significantly restores IL-12p70 responses to IFNgamma/LPS in HE-conditioned BMDM. Our results suggest that oxidant stress induced by free heme may potentially contribute to sustained production of IL-10 and down-regulation of IL-12 responses in malaria.
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PMID:The IL-12p70/IL-10 interplay is differentially regulated by free heme and hemozoin in murine bone-marrow-derived macrophages. 2021 Nov 85


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