Relationship between Anaemia, Haemolysis, Inflammation and Haem Oxygenase-1 at Admission with Sepsis: a pilot study

Ekregbesi, Phebe; Shankar-Hari, Manu; Bottomley, Christian; Riley, Eleanor M.; Mooney, Jason P.

doi:10.1038/s41598-018-29558-5

Cited by 27 publications

(22 citation statements)

References 58 publications

(58 reference statements)

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“…In other words, in addition to defining the pathways leading to neutrophil dysfunction, we also need to identify the point at which the balance tips from these being host protective to increasing the risk to invasive NTS. Importantly, these pathways may contribute to severe bacterial disease even in the absence of malaria infections: in sepsis patients, we have observed that raised concentrations of heme, HO‐1, and IL‐10 are positively correlated with disease severity and mortality . Also, while “invasive” NTS is seen in immunocompromised hosts (such as those with malaria infection), it remains unclear if this is due to increased intestinal invasion, increased dissemination from draining lymph nodes, failure to control systemic bacterial replication, or a combination of any of these.…”

Section: Discussionmentioning

confidence: 93%

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Malaria, anemia, and invasive bacterial disease: A neutrophil problem?

Mooney

Galloway

Riley

2018

Journal of Leukocyte Biology

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Invasive bacterial disease is well described in immunocompromised hosts, including those with malaria infection. One bacterial infection frequently observed in children with Plasmodium falciparum infection is nontyphoidal salmonella (NTS) infection, in which a typically intestinal infection becomes systemic with serious, often fatal, consequences. In this review, we consider the role of malaria‐induced immunoregulatory responses in tipping the balance from tissue homeostasis during malaria infection to risk of invasive NTS. Also, neutrophils are crucial in the clearance of NTS but their ability to mount an oxidative burst and kill intracellular Salmonella is severely compromised during, and for some time after, an acute malaria infection. Here, we summarize the evidence linking malaria and invasive NTS infections; describe the role of neutrophils in clearing NTS infections; review evidence for neutrophil dysfunction in malaria infections; and explore roles of heme oxygenase‐1, IL‐10, and complement in mediating this dysfunction. Finally, given the epidemiological evidence that low density, subclinical malaria infections pose a risk for invasive NTS infections, we consider whether the high prevalence of such infections might underlie the very high incidence of invasive bacterial disease across much of sub‐Saharan Africa.

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Section: Discussionmentioning

confidence: 93%

“…Importantly, these pathways may contribute to severe bacterial disease even in the absence of malaria infections: in sepsis patients, we have observed that raised concentrations of heme, HO-1, and IL-10 are positively correlated with disease severity and mortality. 82…”

Section: Discussionmentioning

confidence: 99%

Malaria, anemia, and invasive bacterial disease: A neutrophil problem?

Mooney

Galloway

Riley

2018

Journal of Leukocyte Biology

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“…Erythrocytes are crucial as they deliver oxygen from lungs to tissues. Sepsis is characterized by a reduction of the red blood cell count and a rapid rise in the WBC count 28,51 . We found that narciclasine could normalize the changes in most of these hematological parameters.…”

Section: Discussionmentioning

confidence: 99%

“…Narciclasine reduces the inflammatory anemia in neonatal rats with sepsis. The development of anemia is common during sepsis and highly prevalent in intensive care patients with high risk of sepsis 28 . We analyzed the whole blood parameters which revealed a significant reduction of RBC, hemoglobin and .…”

Section: Narciclasine Treatment Reduced the Liver Inflammation And Inmentioning

confidence: 99%

Narciclasine improves outcome in sepsis among neonatal rats via inhibition of calprotectin and alleviating inflammatory responses

Kingsley

Bhat

Badhe

et al. 2020

Sci Rep

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Sepsis is associated with exacerbated inflammatory response which subsequently results in multiple organ dysfunction. Sepsis accounts for high mortality and morbidity among newborns worldwide. Narciclasine is a plant alkaloid which has shown to possess anti-inflammatory properties. In this study we investigated the effect and mechanism of action of narciclasine in neonatal sepsis rat models. The excessive release of S100A8/A9 or calprotectin in neonatal sepsis could be detrimental as it could exacerbate the inflammatory responses. We found that narciclasine significantly reduced the plasma levels of S100A8/A9 and also suppressed its expression in the liver and lung. The systemic and local bacterial load was also reduced in the narciclasine treated rats. The systemic and local production of pro-inflammatory cytokines in plasma and organs (liver and lungs) was significantly reduced in the narciclasine treated rats. The histopathological studies showed that narciclasine prevents the organ damage associated with sepsis and improved the survival of neonatal rats. Sepsis increased the phosphorylated NF-κβ p65 protein expression in the liver. Narciclasine suppressed the phosphorylation of nf-κβ p65 and the degradation of NF-κβ inhibitory protein alpha. It could also suppress the expression of adaptor proteins of the toll like receptor signaling pathway viz., myeloid differentiation factor 88 (MyD88), Interleukin-1 receptor-associated kinase 1 (IRAK1) and TNF receptor associated factor 6 (TRAF6). These results suggest that narciclasine protects against sepsis in neonatal rats through the inhibition of calprotectin, pro-inflammatory cytokines and suppression of NF-κβ signaling pathway.Infection is the most important cause of morbidity and mortality in intensive care units worldwide. As the immune response to infection during the neonatal period is mostly immature it is characterized by high rates of morbidity and mortality 1-3 . Most adults are usually able to restrict the bacterial infection whereas neonates are not able to restrict the bacterial infection and develop a severe systemic inflammatory response. Sepsis is a life threatening health condition which occurs due to the severe and systemic inflammatory response to infection. This syndrome starts with dysregulated inflammation, systemic inflammatory response syndrome (SIRS) progressing to severe sepsis and septic shock 4 . It is the most common cause of death in critically ill patients in non-coronary intensive care units 5 .Despite the advancement of medical care, sepsis is one of the leading causes of morbidity and mortality among babies in the neonatal intensive care units 6 . This is mainly due to the non-specific signs and symptoms of neonatal sepsis 2 . Antibiotics and supportive care are the mainstay of treatment at present. The nosocomial pathogens are increasingly becoming resistant to the antimicrobials currently being used. Thus alternative therapeutic options such as anti-inflammatory drugs could be beneficial as neonatal sepsis is characterized by elev...

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“…Ekregbesis and colleagues [83] tested the hypothesis that inflammation-or infection-associated hemolysis contributes to sepsis-associated anemia and also leads to detectable HO1 in plasma. Hemopexin levels were used as one of several parameters of hemolysis.…”

Section: Hpx As a Biomarker For Sepsismentioning

confidence: 99%

What Is Next in This “Age” of Heme-Driven Pathology and Protection by Hemopexin? An Update and Links with Iron

2019

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This review provides a synopsis of the published literature over the past two years on the heme-binding protein hemopexin (HPX), with some background information on the biochemistry of the HPX system. One focus is on the mechanisms of heme-driven pathology in the context of heme and iron homeostasis in human health and disease. The heme-binding protein hemopexin is a multi-functional protectant against hemoglobin (Hb)-derived heme toxicity as well as mitigating heme-mediated effects on immune cells, endothelial cells, and stem cells that collectively contribute to driving inflammation, perturbing vascular hemostasis and blood–brain barrier function. Heme toxicity, which may lead to iron toxicity, is recognized increasingly in a wide range of conditions involving hemolysis and immune system activation and, in this review, we highlight some newly identified actions of heme and hemopexin especially in situations where normal processes fail to maintain heme and iron homeostasis. Finally, we present preliminary data showing that the cytokine IL-6 cross talks with activation of the c-Jun N-terminal kinase pathway in response to heme-hemopexin in models of hepatocytes. This indicates another level of complexity in the cell responses to elevated heme via the HPX system when the immune system is activated and/or in the presence of inflammation.

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Relationship between Anaemia, Haemolysis, Inflammation and Haem Oxygenase-1 at Admission with Sepsis: a pilot study

Cited by 27 publications

References 58 publications

Malaria, anemia, and invasive bacterial disease: A neutrophil problem?

Malaria, anemia, and invasive bacterial disease: A neutrophil problem?

Narciclasine improves outcome in sepsis among neonatal rats via inhibition of calprotectin and alleviating inflammatory responses

What Is Next in This “Age” of Heme-Driven Pathology and Protection by Hemopexin? An Update and Links with Iron

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