Reduction in serum IL‐10 levels is a surrogate marker for predicting vaso‐occlusive crisis in sickle cell disease

Sarray, Sameh; Mahdi, Najat; Saleh, Layal R.; Almaoui, Wassim Y.

doi:10.1002/ajh.23736

Cited by 8 publications

(3 citation statements)

References 7 publications

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“…60 Additional mechanisms responsible for lower PMo numbers may include clearance of apoptotic/necrotic PMos by macrophages in spleen/liver/ bone marrow similar to removal of other senescent/necrotic/ apoptotic circulating blood cells. 61,62 During acute crisis, patients present with an inflammatory cytokine profile, [63][64][65] which may affect PMo survival. However, in severe inflammatory conditions such as sepsis, frequencies of PMo and monocyte numbers are increased (not decreased).…”

Section: Discussionmentioning

confidence: 99%

Patrolling monocytes scavenge endothelial-adherent sickle RBCs: a novel mechanism of inhibition of vaso-occlusion in SCD

Liu

Zhong

Bao

et al. 2019

Blood

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Painful vaso-occlusive crisis (VOC) is the most common complication of sickle cell disease (SCD). Increasing evidence suggests that vaso-occlusion is initiated by increased adherence of sickle red blood cells (RBCs) to the vascular endothelium. Thus, the mechanisms that remove endothelial-attached sickle RBCs from the microvasculature are expected to be critical for optimal blood flow and prevention of VOC in SCD. We hypothesized that patrolling monocytes (PMos), which protect against vascular damage by scavenging cellular debris, could remove endothelial-adherent sickle RBCs and ameliorate VOC in SCD. We detected RBC (GPA+)-engulfed material in circulating PMos of patients with SCD, and their frequency was further increased during acute crisis. RBC uptake by PMos was specific to endothelial-attached sickle, but not control, RBCs and occurred mostly through ICAM-1, CD11a, and CD18. Heme oxygenase 1 induction, by counteracting the cytotoxic effects of engulfed RBC breakdown products, increased PMo viability. In addition, transfusions, by lowering sickle RBC uptake, improved PMo survival. Selective depletion of PMos in Townes sickle mice exacerbated vascular stasis and tissue damage, whereas treatment with muramyl dipeptide (NOD2 ligand), which increases PMo mass, reduced stasis and SCD associated organ damage. Altogether, these data demonstrate a novel mechanism for removal of endothelial attached sickle RBCs mediated by PMos that can protect against VOC pathogenesis, further supporting PMos as a promising therapeutic target in SCD VOC.

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Section: Discussionmentioning

confidence: 99%

Patrolling monocytes scavenge endothelial-adherent sickle RBCs: a novel mechanism of inhibition of vaso-occlusion in SCD

Liu

Zhong

Bao

et al. 2019

Blood

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“…We recently demonstrated a strong association of reduced IL-10 levels with VOC and modulation of VOC-related parameters, namely type, frequency, severity, and duration of VOC, in pediatric SCD patients (25). VOC, and associated osteomyelitis, is a common acute clinical manifestation in children with SCD.…”

Section: Discussionmentioning

confidence: 99%

Contribution of Reduced Interleukin-10 Levels to the Pathogenesis of Osteomyelitis in Children with Sickle Cell Disease

Sarray

Almawi

2015

Clin Vaccine Immunol

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Osteomyelitis is a significant complication of sickle cell disease (SCD), and several factors contribute to its pathogenesis, including altered expression of proinflammatory and anti-inflammatory cytokines. In view of the role of interleukin-10 (IL-10) as an anti-inflammatory cytokine, we tested the notion that SCD osteomyelitis is associated with a reduction in IL-10 secretion and, hence, precipitation of a proinflammatory state. Study subjects comprised 52 SCD patients with confirmed diagnosis of osteomyelitis and 165 age-and gender-matched SCD patients with negative histories of osteomyelitis. Results obtained showed that IL-10 serum levels in SCD osteomyelitis patients were significantly lower than those of control SCD patients. Receiver operating characteristic (ROC) analysis demonstrated that altered IL-10 serum levels predicted the development of osteomyelitis, and the mean area under ROC curves of IL-10 was 0.810 among SCD patients with osteomyelitis. A systematic shift in IL-10 serum levels toward lower values was seen in osteomyelitis cases, with an increased osteomyelitis risk associated with decreased IL-10 levels. Multivariate logistic regression analyses confirmed the independent association of reduced IL-10 with osteomyelitis after controlling for sickle hemoglobin (HbS), fetal hemoglobin (HbF), platelet count, and white blood cell (WBC) count. These data support the strong association of decreased IL-10 levels with osteomyelitis, thereby supporting a role for IL-10 in osteomyelitis follow-up.

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“…Pro-inflammatory cytokines derived from platelets, white blood cells and endothelial cells have all been implicated in the development and main tenance of SCD-associated acute and chronic pain [9][10][11]. Elevation in pro-inflammatory cytokines and reduction in anti-inflammatory cytokine levels have been reported in SCD patients during the vaso-occlusive crisis [12][13][14]. Among the pro-inflammatory cytokines, IL-1 is a pivotal factor controlling the inflammatory response.…”

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confidence: 99%

IL1A rs1800587 Associates with Chronic Noncrisis Pain in Sickle Cell Disease

Jhun

Yao

et al. 2016

Pharmacogenomics

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Aim: Pain is prevalent in sickle cell disease (SCD) patients who display great heterogeneity in pain severity and frequency. Hypothesizing that inflammatory factors are involved in the pathogenesis of SCD pain, we focused on the IL1A C/T polymorphism rs1800587 that is an SNP located in a cis-transcriptional regulatory region. Methods: We genotyped IL1A rs1800587 and performed association studies with phenotype data obtained by a multidimensional pain assessment tool using the PAINReportIt ® Questionnaire. Results: Each T allele was associated with a 3.9 increase in composite pain index score (p = 0.04) as determined by multiple linear regression. Conclusion: IL1A rs1800587 may influence chronic pain in SCD.

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Reduction in serum IL‐10 levels is a surrogate marker for predicting vaso‐occlusive crisis in sickle cell disease

Cited by 8 publications

References 7 publications

Patrolling monocytes scavenge endothelial-adherent sickle RBCs: a novel mechanism of inhibition of vaso-occlusion in SCD

Patrolling monocytes scavenge endothelial-adherent sickle RBCs: a novel mechanism of inhibition of vaso-occlusion in SCD

Contribution of Reduced Interleukin-10 Levels to the Pathogenesis of Osteomyelitis in Children with Sickle Cell Disease

IL1A rs1800587 Associates with Chronic Noncrisis Pain in Sickle Cell Disease

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