Dysregulation of cytokines expression in complicated falciparum malaria with increased TGF-β and IFN-γ and decreased IL-2 and IL-12

Lourembam, Sonia D.; Sawian, Clara E.; Baruah, Satyabrat Malla Bujar

doi:10.1016/j.cyto.2013.08.007

Cited by 22 publications

(22 citation statements)

References 24 publications

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“…balanced cytokine response is being maintained in UM, is reflected in our findings of positive association of IL-10 with TNF-a, IL-1b and TGF-b, and of TGF-b with TNF-a, IL-1b and IFN-g, which is consistent with previous reports from our laboratory and other investigators. 15,16 Interestingly, in SM, IL-10 levels were negatively correlated with parasitemia and the proinflammatory cytokines TNF-a, IL-1b, IFN-g and IL-8. Notably, a study of cytokine networks in Brazilian Amazon also revealed negative correlation of IL-10 with parasitemia in severe Plasmodium vivax malaria, thus suggesting the association to be malaria specific.…”

Section: Discussionmentioning

confidence: 96%

Heightened inflammation in severe malaria is associated with decreased IL-10 expression levels and neutrophils

et al. 2014

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Dysregulation of the cytokine network in severe malaria owing to variations in factors like parasite load, strains and host factors is well documented but the key cytokines that are dysregulated remain poorly elucidated. Longitudinal changes in cytokine levels in an individual with parasitemia and disease resolution is likely to identify the key cytokines. We have analyzed the mRNA expression of cytokines over a 7-d period in severe (SM) and uncomplicated (UM) Plasmodium falciparum malaria. We found up-regulated expression of TNF-α, IL-1β, IFN-γ and TGF-β in SM, with decreased expression of IL-10 on d 0. Further, we observed a negative correlation of IL-10 expression with parasitemia and pro-inflammatory cytokines, suggesting IL-10 to be the key cytokine in tilting the balance to an inflammatory response. Longitudinal analysis revealed that the key cytokines associated with disease were TNF-α, IL-1β, IFN-γ, IL-12α, RANTES and TGF-β, while TNF-α, IL-10 and TGF-β discriminated between SM and UM. A higher neutrophil count in SM and its positive association with parasite density and IL-1β and IL-8 provides support for neutrophils in inflammation in malaria. Our findings suggest subversion of anti-inflammatory response in SM by parasite factors towards an exaggerated pro-inflammatory response with involvement of neutrophils, the classical inflammatory cells.

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Section: Discussionmentioning

confidence: 96%

Heightened inflammation in severe malaria is associated with decreased IL-10 expression levels and neutrophils

et al. 2014

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“…Crucial cytokines in haemoprotozoal disease were not measured in the Goddard study, namely IFN‐γ and TNF‐α. Both of these have been shown to be pivotal mediators of disease in malaria and other Babesia species infections . The Goddard study evaluated cytokine correlations with disease outcome but did not consider the effect of disease severity on cytokine patterns.…”

Section: Discussionmentioning

confidence: 99%

Disease severity and blood cytokine concentrations in dogs with natural Babesia rossi infection

Leisewitz

Goddard

Gier

et al. 2019

Parasite Immunology

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Aims Babesia rossi causes severe disease in dogs. Here, we describe the association between serum cytokine concentrations and disease severity. Methods Seventeen controls and 55 PCR confirmed B rossi‐infected dogs were included. Diseased dogs were subdivided into 23 critically ill and 32 relatively well cases. Serum concentrations of 11 cytokines and biochemical markers of disease severity were determined. Results Significant differences were detected for IL‐6, IL‐8, IL‐10, MCP‐1 and TNF‐α between the groups. Generally, the more complicated the disease, the more pro‐inflammatory the cytokine milieu. IL‐8 showed a reverse trend and was negatively correlated with disease severity. IL‐6, MCP‐1 and TNF‐α were also significantly higher in the dogs that died (n = 9) compared to the dogs that survived (n = 46). IL‐8 showed the opposite. MCP‐1 and TNF‐α were negatively correlated with biochemical markers of severity. Glucose was negatively correlated with IL‐6. Cortisol, peripheral parasite density and band neutrophil count were positively correlated, whilst thyroid hormone was negatively correlated with IL‐6, MCP‐1 and TNF‐α. Conclusions As in malaria and sepsis, B rossi infection induces a pro‐inflammatory cytokine storm that correlates with disease severity and adverse outcome. The multiplicity of cytokines involved argues for redundancy in the system once the disease is established.

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“…Previous studies on the impact of cytokines on clinical outcome in malaria have identified TNF, IFN-γ, IL-1β, IL-6, IL-10, IL-12, transforming growth factor β and IP-10 as important mediators, but data on IL-8in this setting are more limited [20] – [24] . A Zambian study of falciparum malaria patients found no increased levels of IL-8, but the sample size was small, and few patients had severe malaria (8/30) [25] .…”

Section: Discussionmentioning

confidence: 99%

Cytokine Network in Adults with Falciparum Malaria and HIV-1: Increased IL-8 and IP-10 Levels Are Associated with Disease Severity

et al. 2014

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BackgroundCo-infection with malaria and HIV increases the severity and mortality of both diseases, but the cytokine responses related to this co-infection are only partially characterised. The aim of this study was to explore cytokine responses in relation to severity and mortality in malaria patients with and without HIV co-infection.MethodsThis was a prospective cross-sectional study. Clinical data and blood samples were collected from adults in Mozambique. Plasma was analysed for 21 classical pro- and anti-inflammatory cytokines, including interleukins, interferons, and chemokines.ResultsWe included 212 in-patients with fever and/or suspected malaria and 56 healthy controls. Falciparum malaria was diagnosed in 131 patients, of whom 70 were co-infected with HIV-1. The malaria patients had marked increases in their cytokine responses compared with the healthy controls. Some of these changes, particularly interleukin 8 (IL-8) and interferon-γ-inducing protein 10 (IP-10) were strongly associated with falciparum malaria and disease severity. Both these chemokines were markedly increased in patients with falciparum malaria as compared with healthy controls, and raised levels of IL-8 and IP-10 were associated with increased disease severity, even after adjusting for relevant confounders. For IL-8, particularly high levels were found in malaria patients that were co-infected with HIV and in those who died during hospitalization.InterpretationsOur findings underscore the complex role of inflammation during infection with P. falciparum, and suggest a potential pathogenic role for IL-8 and IP-10. However, the correlations do not necessarily mean any causal relationship, and further both clinical and mechanistic research is necessary to elucidate the role of cytokines in pathogenesis and protection during falciparum malaria.

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Dysregulation of cytokines expression in complicated falciparum malaria with increased TGF-β and IFN-γ and decreased IL-2 and IL-12

Cited by 22 publications

References 24 publications

Heightened inflammation in severe malaria is associated with decreased IL-10 expression levels and neutrophils

Heightened inflammation in severe malaria is associated with decreased IL-10 expression levels and neutrophils

Disease severity and blood cytokine concentrations in dogs with natural Babesia rossi infection

Cytokine Network in Adults with Falciparum Malaria and HIV-1: Increased IL-8 and IP-10 Levels Are Associated with Disease Severity

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