Interleukin-27 and interleukin-37 are elevated in sickle cell anemia patients and inhibit in vitro secretion of interleukin-8 in neutrophils and monocytes

Alagbe, Adekunle Emmanuel; Justo, Amauri S.; Ruas, Luciana Pereira; Tonassé, Wouitchékpo Vincent; Santana, Rodrigo Marcionilo; Batista, Thais Helena Chaves; Domingos, Igor F.; Araújo, Aderson S; Bezerra, Marcos André Cavalcanti; Santos, Magnun Nueldo Nunes; Blotta, Maria Heloı́sa Souza Lima

doi:10.1016/j.cyto.2017.12.001

Cited by 16 publications

(15 citation statements)

References 48 publications

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Section: Discussionmentioning

confidence: 94%

“…Previous studies showed that anti-inflammatory cytokines and pro-inflammatory cytokines are elevated in SCD patients compared with controls 21 . Elevation of anti-inflammatory cytokines in response to pro-inflammatory cytokines is sufficient in preventing further cellular or tissue damage but not potent enough to prevent inflammation 21 . Consistent with this, our findings from this study show that anti-inflammatory cytokines (IL-27 and IL-10) as well as pro-inflammatory cytokines (IFNγ) were markedly up-regulated in SCD mice and were rescued with Abx treatment.…”

Section: Discussionmentioning

confidence: 94%

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Depletion of Intestinal Microbiome Partially Rescues Bone Loss in Sickle Cell Disease Male Mice

Tavakoli

Xiao

2019

Sci Rep

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Osteoporosis or osteopenia are common clinical manifestations of sickle cell disease (SCD) with unclear mechanisms. Since senescence of circulating neutrophil can be modulated by signals derived from intestinal microbiome and neutrophils are abundant in bone marrow and can regulate osteoblasts and osteoclasts, we examined whether gut microbiome contributes to bone loss in SCD mice. SCD and their littermates control mice were treated with antibiotics to deplete gut microbiome. At the end of 7 weeks treatment, serum was collected for biochemistry marker measurements. Bone mass and remodeling were evaluated by dual beam X-ray absorptiometry, micro-computed tomography, and histomorphometry. Bone-related genes in tibia and barrier marker genes in the small intestine were analyzed by quantitative PCR. Antibiotic treatment rescued increased intestinal inflammatory cytokine marker genes ( Tnfα , IL17 , Ifnγ ) expression, rescued decreased intestinal barrier marker genes ( claudin 3 and claudin 15 ) expression, and rescued increased serum cytokines (IFNγ, IL27, IL10) in SCD mice. Antibiotic significantly improved decreased bone mass in SCD mice mainly through enhanced osteoblast function and increased osteoblast-related genes ( Runx2 and Igf1 ) expression in SCD mice. Our findings support that increased bacteria load augments antigenic load traversing the impaired intestinal barrier through inflammation, leading to increased inflammatory cytokines, impaired osteoblast function, and bone loss in SCD mice.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 94%

Depletion of Intestinal Microbiome Partially Rescues Bone Loss in Sickle Cell Disease Male Mice

Tavakoli

Xiao

2019

Sci Rep

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“… 10 – 12 Several studies have shown altered levels of some cytokines in SCA patients. 12 – 20 Some found a significantly higher level of TNF-α in SCA patients in VOC and/or during steady state than in healthy HbA controls. 16 – 18 Contrarily, Tavakkoli et al and Graido-Gonzalez et al demonstrated insignificantly elevated TNF-α level in SCA patients in VOC compared with patients in the steady-state group and controls.…”

Section: Introductionmentioning

confidence: 99%

“…Interleukin-8 (IL-8) is a CXC chemokine that stimulates endothelial cell proliferation and angiogenesis through its receptors (CXCR1 and CXCR2), which are expressed mainly by neutrophils. 20 , 22 IL-8 is produced by neutrophils, endothelial cells, macrophages, fibroblasts, and platelets. IL-8 activates re-arrangement of the cytoskeleton, changes in intracellular Ca++ levels, integrins, promotion of protein-granule exocytosis, and respiratory burst in neutrophils.…”

Section: Introductionmentioning

confidence: 99%

Adult Sickle Cell Anaemia Patients in Bone Pain Crisis Have Elevated Pro-Inflammatory Cytokines

Alagbe

Olaniyi

Aworanti

2018

Mediterr J Hematol Infect Dis

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Background and ObjectivesInflammatory markers that influence bone pain crisis (BPC) and other complications of sickle cell anaemia (SCA) are numerous and play various roles. This study determined the plasma levels of tumour necrosis factor (TNF) - α, interleukin - 8 (IL-8), and endothelin - 1 (ET-1) in adult SCA patients during BPC and in steady state. In addition, the plasma levels of these cytokines were correlated with the severity of BPC of the patients.Methods and MaterialsSixty adult SCA patients (30 during BPC and 30 during steady state) and 30 haemoglobin A controls were enrolled for this cross-sectional study. The severity of BPC was assessed clinically, and questionnaires were filled. Plasma levels of TNF- α, IL-8 and ET-1 were quantified by ELISA, and haematological parameters were determined using a 5-part auto-analyzer. Plasma levels were correlated with the severity of bone pain crisis. Results were considered statistically significant if p<0.05.ResultsPlasma TNF-α, IL-8, and ET-1 were significantly elevated in the BPC group than in the steady state group and the controls. Plasma TNF-α, IL-8 and ET-1 were markedly higher in the severe BPC groups than the steady state and control groups, There was a positive correlation between TNF-α and ET-1 in the bone pain crisis group.ConclusionElevated levels of plasma TNF-α, IL-8, and ET-1 further establish the chronic inflammatory state in SCA and equally affirm their significant contribution, not only to pathogenesis but also to the severity of pain in SCA.

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“…Levels of NLRP3 24 and activated cytokines interleukin-1b (IL-1b), IL-6, and IL-8 were significantly elevated in peripheral blood mononuclear cells of patients with SCD. 25 While the role of components of inflammasomes as biomarkers is not known, these molecules could become therapeutic targets. Among the clinically available inflammatory markers, high-sensitivity C-reactive protein has been independently associated with VOCs in children with SCD, predicting a 6.6% increase in frequency of pain crises for every 1-mg/L increase in high-sensitivity C-reactive protein.…”

Section: Sterile Inflammationmentioning

confidence: 99%

Measuring success: utility of biomarkers in sickle cell disease clinical trials and care

Kalpatthi

Novelli

2018

Hematology

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Progress in the care of sickle cell disease (SCD) has been hampered by the extreme complexity of the SCD phenotype despite its monogenic inheritance. While epidemiological studies have identified clinical biomarkers of disease severity, with a few exceptions, these have not been routinely incorporated in clinical care algorithms. Furthermore, existing biomarkers have been poorly apt at providing objective parameters to diagnose sickle cell crisis, the hallmark, acute complication of SCD. The repercussions of these diagnostic limitations are reflected in suboptimal care and scarcity of adequate outcome measures for clinical research. Recent progress in molecular and imaging diagnostics has heralded a new era of personalized medicine in SCD. Precision medicine strategies are particularly timely, since molecular therapeutics are finally on the horizon. This chapter will summarize the existing evidence and promising data on biomarkers for clinical care and research in SCD.

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Interleukin-27 and interleukin-37 are elevated in sickle cell anemia patients and inhibit in vitro secretion of interleukin-8 in neutrophils and monocytes

Cited by 16 publications

References 48 publications

Depletion of Intestinal Microbiome Partially Rescues Bone Loss in Sickle Cell Disease Male Mice

Depletion of Intestinal Microbiome Partially Rescues Bone Loss in Sickle Cell Disease Male Mice

Adult Sickle Cell Anaemia Patients in Bone Pain Crisis Have Elevated Pro-Inflammatory Cytokines

Measuring success: utility of biomarkers in sickle cell disease clinical trials and care

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