The inflammatory cytokine profile of myelodysplastic syndromes

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Abstract

Background:

Accumulating evidence has indicated that the dysregulation of immunological environment has an important role in the pathogenesis of myelodysplastic syndromes (MDS). The previous studies about the levels of the inflammatory cytokines in MDS, such as TNF-α, IFN-γ, IL-6, IL-8, and IL-17, have yielded controversial results. Thus, we performed a meta-analysis to assess the levels of these inflammatory cytokines in MDS.

Methods:

A systematic search in PubMed, MEDLINE, Cochrane Library, Web of Science, CNKI, and CBM was conducted to find eligible studies. Meta-analyses were performed using STATA 12.0 for Windows. Heterogeneity between included studies was assessed by I ² test. We chose SMD as the summary statistic.

Results:

A total of 697 individuals from 11 studies were included in this study. Our results suggest the levels of TNF-α, IL-6, IL-8 were significantly higher in MDS patients compared with controls, SMD and 95%CI was 1.48 (0.60, 2.36), 0.71 (0.16, 1.25) and 0.69 (0.28, 1.09), respectively. Moreover, the levels of IL-17 have decreased in the high-risk MDS, the SMD and 95% CI was 2.96 (0.78, 5.15).

Conclusion:

A close association between immunological microenvironment disorders and the pathogenesis of MDS was revealed in this meta-analysis. More importantly, the profiles of inflammatory cytokines appear to change along the progression of the disease.

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Most cited references 27

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Optimally estimating the sample mean from the sample size, median, mid-range, and/or mid-quartile range

Dehui Luo, Tiejun Tong, Jiming Liu … (2016)

The era of big data is coming, and evidence-based medicine is attracting increasing attention to improve decision making in medical practice via integrating evidence from well designed and conducted clinical research. Meta-analysis is a statistical technique widely used in evidence-based medicine for analytically combining the findings from independent clinical trials to provide an overall estimation of a treatment effectiveness. The sample mean and standard deviation are two commonly used statistics in meta-analysis but some trials use the median, the minimum and maximum values, or sometimes the first and third quartiles to report the results. Thus, to pool results in a consistent format, researchers need to transform those information back to the sample mean and standard deviation. In this article, we investigate the optimal estimation of the sample mean for meta-analysis from both theoretical and empirical perspectives. A major drawback in the literature is that the sample size, needless to say its importance, is either ignored or used in a stepwise but somewhat arbitrary manner, e.g. the famous method proposed by Hozo et al. We solve this issue by incorporating the sample size in a smoothly changing weight in the estimators to reach the optimal estimation. Our proposed estimators not only improve the existing ones significantly but also share the same virtue of the simplicity. The real data application indicates that our proposed estimators are capable to serve as "rules of thumb" and will be widely applied in evidence-based medicine.

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Induction of myelodysplasia by myeloid-derived suppressor cells.

Xianghong Chen, Erika A Eksioglu, Junmin Zhou … (2013)

Myelodysplastic syndromes (MDS) are age-dependent stem cell malignancies that share biological features of activated adaptive immune response and ineffective hematopoiesis. Here we report that myeloid-derived suppressor cells (MDSC), which are classically linked to immunosuppression, inflammation, and cancer, were markedly expanded in the bone marrow of MDS patients and played a pathogenetic role in the development of ineffective hematopoiesis. These clonally distinct MDSC overproduce hematopoietic suppressive cytokines and function as potent apoptotic effectors targeting autologous hematopoietic progenitors. Using multiple transfected cell models, we found that MDSC expansion is driven by the interaction of the proinflammatory molecule S100A9 with CD33. These 2 proteins formed a functional ligand/receptor pair that recruited components to CD33’s immunoreceptor tyrosine-based inhibition motif (ITIM), inducing secretion of the suppressive cytokines IL-10 and TGF-β by immature myeloid cells. S100A9 transgenic mice displayed bone marrow accumulation of MDSC accompanied by development of progressive multilineage cytopenias and cytological dysplasia. Importantly, early forced maturation of MDSC by either all-trans-retinoic acid treatment or active immunoreceptor tyrosine-based activation motif–bearing (ITAM-bearing) adapter protein (DAP12) interruption of CD33 signaling rescued the hematologic phenotype. These findings indicate that primary bone marrow expansion of MDSC driven by the S100A9/CD33 pathway perturbs hematopoiesis and contributes to the development of MDS.

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Protumor vs antitumor functions of IL-17.

Bhaskar Saha, Gopal Murugaiyan (2009)

Inflammation appears to be a necessity for both metastasis and elimination of tumor cells. IL-17, a proinflammatory cytokine produced by Th17 cells, contributes to both the processes by playing a dual role in the antitumor immunity. On one hand, IL-17 promotes an antitumor cytotoxic T cell response leading to tumor regression. On the other hand, by facilitating angiogenesis and egress of tumor cells from the primary focus, IL-17 promotes tumor growth. Thus, the therapeutic application that uses IL-17 needs to be refined by minimizing its protumor functions.

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Author and article information

Journal

Journal ID (nlm-ta): Medicine (Baltimore)

Journal ID (iso-abbrev): Medicine (Baltimore)

Journal ID (publisher-id): MEDI

Title: Medicine

Publisher: Wolters Kluwer Health

ISSN (Print): 0025-7974

ISSN (Electronic): 1536-5964

Publication date Collection: May 2019

Publication date (Electronic): 31 May 2019

Volume: 98

Issue: 22

Electronic Location Identifier: e15844

Affiliations

Department of Hematology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, China.

Author notes

[∗ ]Correspondence: Baoxia Dong, (e-mail: dongbaoxia@ 123456hotmail.com ), Xiequn Chen, Department of Hematology, Xijing Hospital, Fourth Military Medical University, No 127 Chang’le West Road, Xi’an 710032, Shaanxi, China (e-mail: xiequnchen@ 123456fmmu.edu.cn ).

Article

Publisher ID: MD-D-18-09433 Accession ID: 15844

DOI: 10.1097/MD.0000000000015844

PMC ID: 6708708

PubMed ID: 31145332

SO-VID: 3ec7d31e-80a2-4e43-99d0-2087ae5d706b

License:

This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc/4.0

History

Date received : 14 December 2018

Date revision received : 23 April 2019

Date accepted : 6 May 2019

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Keywords: ifn-γ,il-17,il-6,il-8,meta-analysis,myelodysplastic syndromes,tnf-α

Data availability:

Keywords: ifn-γ, il-17, il-6, il-8, meta-analysis, myelodysplastic syndromes, tnf-α

The inflammatory cytokine profile of myelodysplastic syndromes : A meta-analysis

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Most cited references 27

Optimally estimating the sample mean from the sample size, median, mid-range, and/or mid-quartile range

Induction of myelodysplasia by myeloid-derived suppressor cells.

Protumor vs antitumor functions of IL-17.

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