Plasma levels of interleukin‐18 and interleukin‐12 in <i>Plasmodium falciparum</i> malaria

Malaguarnera, Mariano; Pignatelli, Salvatore; Musumeci, Maria; Simporé, Jacques; Musumeci, Salvatore

doi:10.1046/j.1365-3024.2002.00485.x

Cited by 31 publications

(49 citation statements)

References 17 publications

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“…Although IL-23 and IL-12 share the p40 subunit [17], levels of IL-23 were elevated in children with malarial anemia, while plasma IL-12 concentrations progressively declined with increasing anemia severity. The decrease in IL-12 with increasing disease severity parallels previous findings in African children residing in areas with intense malaria transmission [12][13][14]29,[43][44][45]. In addition, examination of the IL-12 to IL-23 ratio revealed that SMA is characterized by low levels of IL-12 relative to IL-23.…”

Section: Discussionsupporting

confidence: 82%

Increased circulating interleukin (IL)-23 in children with malarial anemia: In vivo and in vitro relationship with co-regulatory cytokines IL-12 and IL-10

Ong’echa

Remo

Kristoff

et al. 2008

Clinical Immunology

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Severe malarial anemia (SMA) is a leading cause of mortality among children in sub-Saharan Africa. Although the novel cytokine, interleukin (IL)-23, promotes anemia in chronic inflammatory diseases, the role of IL-23 in SMA remains undefined. Since IL-23 and IL-12 share the IL-12p40 subunit and IL-12Rβ1 receptor, and are down-regulated by IL-10, relationships among these cytokines were explored in Kenyan children with varying severities of malarial anemia. Children with malarial anemia had increased circulating IL-23 and IL-10, and decreased IL-12 relative to healthy controls. Enhanced anemia severity and elevated parasitemia were associated with increased IL-10 relative to IL-23 and IL-12. Further exploration of the relationships among the cytokines using an in vitro model in which peripheral blood mononuclear cells were treated with synthetic hemozoin (sHz, malarial pigment) revealed that IL-12p35 and IL-23p19 transcripts had a sustained induction over 72 hrs, while IL-12p40 and IL-10 message peaked at 24 hrs, and rapidly declined thereafter. Taken together, results here show that IL-23 is elevated in children with malarial anemia, and that IL-10 and IL-12 appear to have important regulatory effects on IL-23 production during childhood malaria.

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Section: Discussionsupporting

confidence: 82%

Increased circulating interleukin (IL)-23 in children with malarial anemia: In vivo and in vitro relationship with co-regulatory cytokines IL-12 and IL-10

Ong’echa

Remo

Kristoff

et al. 2008

Clinical Immunology

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“…Other cytokines that may also be produced during malaria are IL-12, IL-18, and migratory inhibitory factor (MIF). The first two are secreted from macrophages and stimulate natural killer cells as well as B and T cells to produce IFN-␥ (34, 103,104). In B cells, IL-12 also seems to stimulate antibody production.…”

Section: Dyserythropoiesis and Immune-mediated Anemiamentioning

confidence: 99%

Potential Immune Mechanisms Associated with Anemia in Plasmodium vivax Malaria: a Puzzling Question

et al. 2014

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The pathogenesis of malaria is complex, generating a broad spectrum of clinical manifestations. One of the major complications and concerns in malaria is anemia, which is responsible for considerable morbidity in the developing world, especially in children and pregnant women. Despite its enormous health importance, the immunological mechanisms involved in malaria-induced anemia remain incompletely understood. Plasmodium vivax, one of the causative agents of human malaria, is known to induce a strong inflammatory response with a robust production of immune effectors, including cytokines and antibodies. Therefore, it is possible that the extent of the immune response not only may facilitate the parasite killing but also may provoke severe illness, including anemia. In this review, we consider potential immune effectors and their possible involvement in generating this clinical outcome during P. vivax infections.

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“…In contrast, patients with acute disease and elevated levels of IL-12 had marked increases in IL-10. 83 Since the majority of patients with anemia in this last study had average Hb levels of 90 g/L (9 g/dL) it is possible that, as with mice, increases in IL-12 are associated with reduced severity of SMA. The data on serum levels of MIF in patients with malaria are, however, consistent with its role as a hematopoietic suppressor in mice: MIF concentrations in those with moderate anemia are decreased, 89 and MIF is elevated in patients with more severe anemia.…”

Section: Org Frommentioning

confidence: 77%

“…In humans, the secretion of IL-12 and IL-18 from macrophages induces production of IFN-␥ from natural killer (NK), B cells, and T cells, 83 while MIF is produced by activated T cells and macrophages and inhibits the anti-inflammatory activity of glucocorticoids (for review see Clark and Cowden 84 ).…”

Section: Erythropoietic Suppression and Dyserythropoiesismentioning

confidence: 99%

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Malarial anemia: of mice and men

Lamikanra

Brown²,

Potocnik³

et al. 2007

Blood

228

215

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Severe malaria is manifest by a variety of clinical syndromes dependent on properties of both the host and the parasite. In young infants, severe malarial anemia (SMA) is the most common syndrome of severe disease and contributes substantially to the considerable mortality and morbidity from malaria. There is now growing evidence, from both human and mouse studies of malaria, to show that anemia is due not only to increased hemolysis of infected and clearance of uninfected red blood cells (RBCs) but also to an inability of the infected host to produce an adequate erythroid response. In this review, we will summarize the recent clinical and experimental studies of malaria to highlight similarities and differences in human and mouse pathology that result in anemia and so inform the use of mouse models in the study of severe malarial anemia in humans. Malaria in humansThe vast majority of morbidity and mortality from malaria is caused by infection with Plasmodium falciparum, although P vivax, P ovale, and P malariae also are responsible for human infections. The total burden of disease has recently been estimated to 515 million episodes annually and malaria is responsible for 18% of all childhood deaths in sub-Saharan Africa, equivalent to 800 000 deaths each year. 1,2 The study of malarial anemia has somewhat belatedly excited academic and professional interest. Severe malarial anemia (SMA) certainly merits concern as a major public health problem because of the very large numbers of children affected, and it is likely that these numbers may increase as drug resistance spreads. Concerns have also been raised by data from recent vaccine studies, which suggest that monkeys immunized with erythrocytic-stage antigens, and that have acquired protection from acute infection, may succumb to severe anemia during a subacute or chronic phase of infection. 3,4 Moreover, there is increasing awareness of the difficulty of satisfactory treatment by blood transfusion outside specialist centers in many endemic areas as a result of the limited availability of a rapid and safe supply of blood. 1,5 SMA is seen most frequently in areas of very high malaria transmission and most commonly in young children and pregnant women. 6 The prevalence of anemia, defined as a hematocrit (Hct) level higher than 0.33, in malaria-endemic areas of Africa, varies between 31% and 91% in children, and between 60% and 80% in pregnant women. 7,8 Given the high degree of morbidity that is associated with SMA in children, this term will be used to refer to severe anemia in this group, unless stated otherwise.It is very difficult to determine the number of cases of severe anemia attributable to malaria as the WHO definition of SMA (a hemoglobin [Hb] concentration of Ͻ 50 g/L [5 g/dL], or a Hct Ͻ 0.15, in the presence of a parasitemia Ͼ 10 000 parasites per microliter [L], and a normocytic blood film) may exclude the considerable proportion of children admitted with severe anemia that has a blood smear negative for malaria parasites but that responds to an...

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Plasma levels of interleukin‐18 and interleukin‐12 in Plasmodium falciparum malaria

Cited by 31 publications

References 17 publications

Increased circulating interleukin (IL)-23 in children with malarial anemia: In vivo and in vitro relationship with co-regulatory cytokines IL-12 and IL-10

Increased circulating interleukin (IL)-23 in children with malarial anemia: In vivo and in vitro relationship with co-regulatory cytokines IL-12 and IL-10

Potential Immune Mechanisms Associated with Anemia in Plasmodium vivax Malaria: a Puzzling Question

Malarial anemia: of mice and men

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