Elevated serum levels of IL-1ra in children with Plasmodium falciparum malaria are associated with increased severity of disease

John, Chandy C.; Park, Gregory S.; Sam-Agudu, Nadia A.; Opoka, Robert O.; Boivin, Michael J.

doi:10.1016/j.cyto.2007.12.008

Cited by 47 publications

(55 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The early inflammatory response to HZ was first triggered by enhanced IL-1␤ transcription 0 to 2 h after HZ phagocytosis ended and then reinforced (4 h after phagocytosis) by increased expression of MMP-9, TNF-␣, and IL-1RA, a cytokine that was recently connected to increased severity of cerebral malaria (CM) (25). At this time, either macroarray analysis or real-time RT-PCR also detected enhanced expression of several molecules belonging to the chemokine class, a vast family of chemoattractant molecules involved in monocyte migration and neutrophil recruitment (see reference 30 for a review).…”

Section: Discussionmentioning

confidence: 99%

Involvement of Inflammatory Chemokines in Survival of Human Monocytes Fed with Malarial Pigment

et al. 2010

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Involvement of Inflammatory Chemokines in Survival of Human Monocytes Fed with Malarial Pigment

et al. 2010

View full text Add to dashboard Cite

“…The discovery of a reliable laboratory test that accurately identifies individuals at risk of developing fatal CM would be a valuable tool. Human studies have revealed tight association between levels of specific chemokines and CM mortality [4,5,12,41,[43][44][45]67]. Thus, understanding the alterations in cytokine or chemokine homeostasis in CM patients will elucidate the underlying pathogenesis and identify potential predictive prognostic biomarkers for CM mortality.…”

Section: Discussionmentioning

confidence: 99%

CXCL4 and CXCL10 Predict Risk of Fatal Cerebral Malaria

et al. 2011

View full text Add to dashboard Cite

Abstract. Plasmodium falciparum in a subset of patients can lead to a diffuse encephalopathy known as cerebral malaria (CM). Despite treatment, mortality caused by CM can be as high as 30% while 10% of survivors of the disease may experience shortand long-term neurological complications. The pathogenesis of CM involves alterations in cytokine and chemokine expression, local inflammation, vascular injury and repair processes. These diverse factors have limited the rate of discovery of prognostic predictors of fatal CM. Identification of reliable early predictors of CM severity will enable clinicians to adjust this risk with appropriate management of CM. Recent studies revealed that elevated levels of CXCL10 expression in cerebrospinal fluid and peripheral blood plasma independently predicted severe and fatal CM. CXCR3, a promiscuous receptor of CXCL10, plays an important role in pathogenesis of mouse model of CM. In this study the role of corresponding CXCR3 ligands (CXCL11, CXCL10, CXCL9 & CXCL4) in fatal or severe CM was evaluated by comparing their levels in 16 healthy control (HC), 26 mild malaria (MM), 26 cerebral malaria survivors (CMS) and 12 non-survivors (CMNS) using enzyme linked immunosorbent assay (ELISA). Levels of CXCL4 and CXCL10 were significantly elevated in CMNS patients (p < 0.05) when compared with HC, MM and CMS. Elevated plasma levels of CXCL10 and CXCL4 were tightly associated with CM mortality. Receiver Operating Characteristic (ROC) curve analysis revealed that CXCL4 and CXCL10 can discriminate CMNS from MM (p < 0.0001) and CMS (p < 0.0001) with an area under the curve (AUC) = 1. These results suggest that CXCL4 and CXCL10 play a prominent role in pathogenesis of CM associated death and may be used as functional or surrogate biomarkers for predicting CM severity.

show abstract

“…These observations attracted interest in investigating the trafficking pathways by which these cells are recruited to target organs and the potential contribution of chemokines to severe malaria (13). Recent studies revealed that circulating levels of various chemokines, including CCL4, CXCL4, CXCL8, and CXCL10 (also known as IFN-g-inducible protein 10), are significantly elevated in CM cases compared with mild malaria cases or healthy control individuals (14)(15)(16)(17)(18). Among these chemokines, CXCL10 appears to be the most accurate predictor of CM mortality (15,18).…”

mentioning

confidence: 99%

Monocyte- and Neutrophil-Derived CXCL10 Impairs Efficient Control of Blood-Stage Malaria Infection and Promotes Severe Disease

Ioannidis

Nie

et al. 2016

The Journal of Immunology

View full text Add to dashboard Cite

CXCL10, or IFN-γ–inducible protein 10, is a biomarker associated with increased risk for Plasmodium falciparum–mediated cerebral malaria (CM). Consistent with this, we have previously shown that CXCL10 neutralization or genetic deletion alleviates brain intravascular inflammation and protects Plasmodium berghei ANKA-infected mice from CM. In addition to organ-specific effects, the absence of CXCL10 during infection was also found to reduce parasite biomass. To identify the cellular sources of CXCL10 responsible for these processes, we irradiated and reconstituted wild-type (WT) and CXCL10−/− mice with bone marrow from either WT or CXCL10−/− mice. Similar to CXCL10−/− mice, chimeras unable to express CXCL10 in hematopoietic-derived cells controlled infection more efficiently than WT controls. In contrast, expression of CXCL10 in knockout mice reconstituted with WT bone marrow resulted in high parasite biomass levels, higher brain parasite and leukocyte sequestration rates, and increased susceptibility to CM. Neutrophils and inflammatory monocytes were identified as the main cellular sources of CXCL10 responsible for the induction of these processes. The improved control of parasitemia observed in the absence of CXCL10-mediated trafficking was associated with a preferential accumulation of CXCR3+CD4+ T follicular helper cells in the spleen and enhanced Ab responses to infection. These results are consistent with the notion that some inflammatory responses elicited in response to malaria infection contribute to the development of high parasite densities involved in the induction of severe disease in target organs.

show abstract

Elevated serum levels of IL-1ra in children with Plasmodium falciparum malaria are associated with increased severity of disease

Cited by 47 publications

References 17 publications

Involvement of Inflammatory Chemokines in Survival of Human Monocytes Fed with Malarial Pigment

Involvement of Inflammatory Chemokines in Survival of Human Monocytes Fed with Malarial Pigment

CXCL4 and CXCL10 Predict Risk of Fatal Cerebral Malaria

Monocyte- and Neutrophil-Derived CXCL10 Impairs Efficient Control of Blood-Stage Malaria Infection and Promotes Severe Disease

Contact Info

Product

Resources

About