Serum IL-6, IL-10, and TNFα levels in pediatric sickle cell disease patients during vasoocclusive crisis and steady state condition

Sarray, Sameh; Saleh, Layal R.; Saldanha, Fabiola Lisa; Al-Habboubi, Hebah H.; Mahdi, Najat; Almawi, Wassim Y.

doi:10.1016/j.cyto.2014.11.030

Cited by 67 publications

(56 citation statements)

References 34 publications

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“…Interestingly, many inflammatory cytokines that are involved in neurogenic inflammation are significantly increased in patients with SCD compared to controls, and increase further during acute vaso-occlusive crisis. (Francis & Haywood 1992; Keikhaei et al , 2013; Pathare et al , 2004; Sarray et al , 2015) Our data support the need for further study into the downstream effects of chronic SP elevation in baseline health and further SP elevation during acute pain. In addition, risk factors and reasons for increased SP levels in patients with SCD require further investigation.…”

Section: Discussionsupporting

confidence: 64%

Substance P is increased in patients with sickle cell disease and associated with haemolysis and hydroxycarbamide use

et al. 2016

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Summary Sickle cell disease (SCD) pain transitions from acute to chronic for unknown reasons. Chronic elevation of the pain neurotransmitter substance P (SP) sensitizes pain nociceptors. We evaluated SP levels in controls and SCD patients during baseline and acute pain and investigated associations between SP and age, gender, pain history, haemolysis and hydroxycarbamide (also termed hydroxyurea) use. Plasma SP levels were measured using enzyme-linked immunosorbent assay. Independent samples t-test compared SP levels between: 1) SCD baseline and controls and 2) SCD baseline and acute pain. Multivariate linear regression determined associations between SP and age, gender, pain history and hydroxycarbamide use. Spearman correlation determined an association between SP and haemolysis. We enrolled 35 African American controls, 25 SCD baseline and 12 SCD pain patients. SCD patients were 7-19 years old. Mean±standard deviation SP level (pg/ml) in SCD baseline was higher than controls (32.4±11.6 vs. 22.9±7.6, P=0.0009). SP in SCD pain was higher than baseline (78.1±43.4 vs. 32.4±11.6, P=0.004). Haemolysis correlated with increased SP: Hb (r=−0.7, P=0.0002), reticulocyte count (r=0.61, P=0.0016), bilirubin (r=0.68, P=0.0216), LDH (r=0.62, P=0.0332), aspartate aminotransferase (r=0.68, P=0.003). Patients taking hydroxycarbamide had increased SP (β=29.2, P=0.007). SP could be a mediator of or marker for pain sensitization in SCD and a biomarker and/or target for novel pain treatment.

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Section: Discussionsupporting

confidence: 64%

Substance P is increased in patients with sickle cell disease and associated with haemolysis and hydroxycarbamide use

et al. 2016

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“…In SCD, the chronic inflammation is characterized by increased leukocytes count and activation of granulocytes, monocytes, and platelets [9,10,14]. Proinflammatory mediators derived from leukocytes, platelets and endothelial cells, such as tumor necrosis factor alpha (TNF-α) and the interleukins (IL), IL-6, IL-1β and IL-8, are usually higher in SCD [15–17]. The increased production and release of proinflammatory cytokines can favor the vaso-occlusive process due to endothelial activation, erythrocytes and leukocytes adhesion to vascular endothelial and endothelial cells apoptosis [15,18].…”

Section: Introductionmentioning

confidence: 99%

Inflammation in Sickle Cell Disease: Differential and Down-Expressed Plasma Levels of Annexin A1 Protein

et al. 2016

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Sickle cell disease (SCD) is an inherited hemolytic anemia whose pathophysiology is driven by polymerization of the hemoglobin S (Hb S), leading to hemolysis and vaso-occlusive events. Inflammation is a fundamental component in these processes and a continuous inflammatory stimulus can lead to tissue damages. Thus, pro-resolving pathways emerge in order to restore the homeostasis. For example there is the annexin A1 (ANXA1), an endogenous anti-inflammatory protein involved in reducing neutrophil-endothelial interactions, accelerating neutrophil apoptosis and stimulating macrophage efferocytosis. We investigated the expression of ANXA1 in plasma of SCD patients and its relation with anemic, hemolytic and inflammatory parameters of the disease. Three SCD genotypes were considered: the homozygous inheritance for Hb S (Hb SS) and the association between Hb S and the hemoglobin variants D-Punjab (Hb SD) and C (Hb SC). ANXA1 and proinflammatory cytokines were quantified by ELISA in plasma of SCD patients and control individuals without hemoglobinopathies. Hematological and biochemical parameters were analyzed by flow cytometry and spectrophotometer. The plasma levels of ANXA1 were about three-fold lesser in SCD patients compared to the control group, and within the SCD genotypes the most elevated levels were found in Hb SS individuals (approximately three-fold higher). Proinflammatory cytokines were higher in SCD groups than in the control individuals. Anemic and hemolytic markers were higher in Hb SS and Hb SD genotypes compared to Hb SC patients. White blood cells and platelets count were higher in Hb SS genotype and were positively correlated to ANXA1 levels. We found that ANXA1 is down-regulated and differentially expressed within the SCD genotypes. Its expression seems to depend on the inflammatory, hemolytic and vaso-occlusive characteristics of the diseased. These data may lead to new biological targets for therapeutic intervention in SCD.

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“…A number of reports have documented enhanced steady state levels of inflammation in SCD patients compared to healthy controls [51;55;58;64]. These differences typically include elevated cytokines (e.g., TNFα, IL-6, IFN-γ, and IL-1β) as well as elevations in vasoactive peptides (e.g., endothelin) and neuropeptides (e.g., substance P) implicated in pain transmission [64], although results are not uniform [33;61]. While SCD participants were carefully selected to be outside of a crisis, most reported ongoing, mild pain at the time of testing, a finding that is common in adult SCD patients [65].…”

Section: Discussionmentioning

confidence: 99%

“…TNFα and NPY were of particular interest in the current study due to their potential role in pain sensitivity [4;9;47;61;63;66]. Pro-inflammatory cytokine levels such as IL-6 and TNF-α correlate with intensity of pain among samples of arthritis, back pain, and fibromyalgia patients [26;41;53;56;69].…”

Section: Discussionmentioning

confidence: 99%

Quantitative sensory testing and pain-evoked cytokine reactivity

Campbell

Carroll

Kiley

et al. 2016

Pain

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Sickle cell disease (SCD) is an inherited blood disorder associated with significant morbidity, which includes severe episodic pain, and, often, chronic pain. Compared to healthy individuals, patients with SCD report enhanced sensitivity to thermal detection and pain thresholds and have altered inflammatory profiles, yet no studies to date have examined biomarker reactivity following laboratory-induced pain. We sought to examine this relationship in SCD patients compared to healthy control participants. We completed quantitative sensory testing (QST) in 83 patients with SCD and sequential blood sampling in 27 of them, whom we matched (sex, age, race, BMI, education) to 27 healthy controls. Surprisingly, few QST differences emerged between groups. Heat pain tolerance, pressure pain threshold at the trapezius, thumb and quadriceps, and thermal temporal summation at 45°C differed between groups in the expected direction, while conditioned pain modulation and pain ratings to hot water hand immersion were counterintuitive, possibly due to tailoring the water temperature to a perceptual level; SCD patients received milder temperatures. In the matched subsample, group differences and group by time interactions were observed in biomarkers including TNFα, IL-1β, IL-4, and NPY. These findings highlight the utility of laboratory pain testing methods for understanding individual differences in inflammatory cytokines. Our findings suggest amplified pain-evoked pro-inflammatory cytokine reactivity among patients with SCD relative to carefully matched controls. Future research is warranted to evaluate the impact of enhanced pain-related cytokine response and whether it is predictive of clinical characteristics and the frequency/severity of pain crises in SCD patients.

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Serum IL-6, IL-10, and TNFα levels in pediatric sickle cell disease patients during vasoocclusive crisis and steady state condition

Cited by 67 publications

References 34 publications

Substance P is increased in patients with sickle cell disease and associated with haemolysis and hydroxycarbamide use

Substance P is increased in patients with sickle cell disease and associated with haemolysis and hydroxycarbamide use

Inflammation in Sickle Cell Disease: Differential and Down-Expressed Plasma Levels of Annexin A1 Protein

Quantitative sensory testing and pain-evoked cytokine reactivity

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