High levels of proinflammatory cytokines IL-6 and IL-8 are associated with a poor clinical outcome in sickle cell anemia

Ribeiro

Mediators of Inflammation

et al. 2020

Recent evidence suggests that abnormalities involving CD4+T lymphocytes are associated with the pathophysiology of osteonecrosis (ON); however, few studies have addressed the CD4+T cells in ON related to sickle cell disease (SCD/ON). In addition, T cells producing multiple cytokines simultaneously are often present in the inflammatory milieu and may be implicated in the immune response observed in SCD/ON. In the present study, we aimed to characterize the functional status of CD4+T cells in SCD by simultaneously determining the frequency of IFN-γ+, IL-4+, and IL-17+ CD4+T in cell cultures under exogenous stimuli. Peripheral blood mononuclear cells (PB-MNCs) from 9 steady-state SCD patients, 15 SCD/ON patients, and 19 healthy controls had functional status of CD4+T cells analyzed. Bone marrow mononuclear cells (BM-MNCs) from 24 SCD/ON patients (SCD BM) and 18 patients with ON not related to SCD (non-SCD BM) were also analyzed. We found that PB-MNC of SCD patients with or without ON presented significantly reduced TCD4+, TCD8+, and TCD4+ naïve cell frequencies and increased frequency of circulating CD4+T cells able to simultaneously produce IFN-γ+/IL4+ and IL-17+/IL4+ compared to healthy controls. Conversely, the polyclonal stimulation of BM-MNC induced an increased frequency of CD4+IFN-γ+ and CD4+IL-17+ in SCD BM compared to non-SCD BM. The increased proportion of CD4+ T cells able to produce a broad spectrum of proinflammatory cytokines after a strong stimulus indicates that the immune system in SCD/ON patients presents an expressive pool of partially differentiated cells ready to take on effector function. It is possible that this increased subpopulation may extend to inflammatory sites of target organs and may contribute to the maintenance of inflammation and the pathophysiology of osteonecrosis in sickle cell disease.

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

CD4⁺ T Cell Profile and Activation Response in Sickle Cell Disease Patients with Osteonecrosis

Ribeiro

Mediators of Inflammation

et al. 2020

“…High serum levels of pro-in ammatory and T-helper 17 cells related-cytokines (IL-6, IL-17A, IL-22 and IL- 23) have all been strongly associated with increased risk of developing leg ulcers in sickle cell disease [15,16].…”

Section: Introductionmentioning

confidence: 99%

Leg Ulcers in Sickle Cell Disease: a protocol for systematic review and meta-analysis

Duru

Ukoma

Okoye

et al. 2020

Preprint

Background: Sickle cell disease affects about 112 per 100,000 live births globally. Leg ulcer is a major and clinically challenging complication of sickle cell disease. It affects about 1.0 -75 % of SCDs with exact prevalence unknown. This study aims to determine pooled prevalence of leg ulcer in sickle cell disease as well as evaluate moderating effects of single nucleotide polymorphisms, patient’s age and sex, geographical locations, treatment modalities and expression of plasma cytokines.Methods: A search strategy is developed using MeSH, text words and entry terms. Nine databases will be searched: PuMed, African Journal Online, Embase, Google Scholar, Scopus, Cochrane Library, CINAHL, Web of Science and ResearchGate. Only observational studies, retrievable in the English language will be included. The primary outcome is the proportion of leg ulcers in sickle cell disease. The effect size is prevalence. Identified studies will be screened and selected based on inclusion criteria using EndNote version 9. Quality scores and risk of bias for individual studies will be reported. Studies will be assessed for methodological, clinical, and statistical heterogeneity. Funnel Plots will be used to assess publication bias. Extracted data items will be arranged in Microsoft Excel before exporting them to CMA software for quantitative analysis. The random model computation for pooled effect size will be used. Results including pooled prevalence, standard error, 95 % CI and subgroup analysis will be presented in forest plots. Discussion: Ethical approval will not be required since this study is based on published data. This protocol will enable reproducible and accurate estimation of pooled prevalence of leg ulcers and effects of moderators in sickle cell disease. The data from such review will stimulate further research into leg ulcers in SCD. The final report of this study will be published in a peer-reviewed journal and the findings will be made available to various health experts that manage SCD patients especially haematologists.Trial Registration Number: This protocol is registered in PROSPERO; with registration number CRD42020213310.

Food Science & Nutrition

Anti‐inflammatory effects of kawakawa (Piper excelsum): An integrative mRNA–miRNA approach

Tautuiaki,

Gojer,

Jayaprakash

et al. 2024

Kawakawa (Piper excelsum) is an endemic medicinal plant widely consumed by Māori in New Zealand. Presence of diverse biologically active phytochemicals in kawakawa may underpin its putative therapeutic anti‐inflammatory properties. However, no human studies on its anti‐inflammatory effects are yet undertaken. Blood samples from a randomized controlled dietary intervention exploring the impact of kawakawa compared to control on postprandial microRNAs (miRNA) abundances and their respective gene and protein targets in a cohort of healthy human volunteers (n = 26; Age; 33.6 ± 1.9 year and BMI; 22.5 ± 0.4 kg/m2) were analyzed. Postprandial levels of nine miRNAs showed differential abundances; hsa‐miR‐17‐5p, ‐21‐5p, ‐320a‐5p, let‐7g‐5p, ‐16‐5p, ‐122‐5p, and ‐144‐3p was upregulated while as hsa‐miR‐221‐3p and ‐223‐3p was downregulated in response to kawakawa compared to control. In silico analysis indicated enrichment of miRNAs in multiple inflammation‐related pathways, including apoptosis, cytokine signaling, MAPK signaling, and MTOR pathways. Furthermore, gene expression of IL‐8 (p = .03), IL‐6 (p = .01), and PPAR‐γ were significantly reduced following kawakawa intake compared to control. While as plasma IL‐6 showed a significant increase over 120 min in the kawakawa arm. These results highlight kawakawa to exert anti‐inflammatory effects by modulating the expression of miRNAs and their target genes and proteins in the inflammatory signaling pathways.