Interleukin-17 enhances the production of interferon-γ and tumour necrosis factor-α by bone marrow T lymphocytes from patients with lower risk myelodysplastic syndromes.

Abstract

INTRODUCTION:

Lower risk myelodysplastic syndromes (MDSs) are characterised by increased apoptosis of haematopoietic cells in the bone marrow (BM). The mechanism driving this excessive apoptosis involves multiple immune molecules, including inflammatory cytokines such as interferon-γ (IFN-γ), tumour necrosis factor-α (TNF-α) and interleukins (ILs). Interleukin-17 (IL-17) is the hallmark cytokine produced by CD4(+) Th17 cells, and IL-17 mediates activation of the adaptive T-cell response inducing an inflammatory cytokine environment. However, little is known about the role of IL-17 in MDS-associated immune dysfunction.

METHODS:

A total of 47 patients with myelodysplastic syndromes were enrolled in this study, and the levels of IL-17 and IL-17 receptor (IL-17R) in BM mononuclear cells (BMNCs) were detected by real-time polymerase chain reaction (RQ-PCR) and enzyme-linked immunosorbent assay (ELISA). Then, BMNCs were stimulated with recombinant human IL-17 (rhIL-17), and flow cytometry was used to analyse the production of IFN-γ and TNF-α by CD4(+) and CD(+) T lymphocytes from patients with lower-risk MDS. Characterisation of IL-17 expression in patients with the HLA-DR15 allele or hypocellularity was also performed.

RESULTS:

mRNA levels for both IL-17 and the IL-17R subunits in BMNCs and for IL-17 in the BM and plasma were higher in patients with lower-risk MDS as compared to patients with higher-risk MDS and normal controls. The production of IFN-γ and TNF-α by CD4(+) and CD8(+) T lymphocytes from patients with lower-risk MDS could be enhanced by recombinant human IL-17 (rhIL-17) treatment. Furthermore, increased IL-17 expression was associated with more severe anaemia in with patients with MDS.

CONCLUSION:

Elevated IL-17 levels and IL-17-induced IFN-γ and TNF-α overproduction may be involved in the pathogenesis of lower risk MDS.

• Authors: Zheng Zhang, Xiao Li, Juan Guo, Feng Xu, Qi He, Youshan Zhao, Yujuan Yang, Shucheng Gu, Yan Zhang, Lingyun Wu, Chunkang Chang
• Journal: European journal of haematology (Eur J Haematol) Vol. 90 Issue 5 Pg. 375-84 (May 2013) ISSN: 1600-0609 [Electronic] England
• PMID: 23331180 (Publication Type: Journal Article)
• Copyright: © 2013 John Wiley & Sons A/S.

Chemical References

• HLA-DR Serological Subtypes
• HLA-DR15 antigen
• Interleukin-17
• RNA, Messenger
• Receptors, Interleukin-17
• Tumor Necrosis Factor-alpha
• Interferon-gamma

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Alleles
• Anemia (etiology)
• Bone Marrow Cells (drug effects, immunology, metabolism)
• Female
• HLA-DR Serological Subtypes (genetics, immunology)
• Humans
• Interferon-gamma (biosynthesis)
• Interleukin-17 (genetics, metabolism, pharmacology)
• Male
• Middle Aged
• Myelodysplastic Syndromes (complications, genetics, immunology, metabolism)
• RNA, Messenger (genetics, metabolism)
• Receptors, Interleukin-17 (genetics, metabolism)
• T-Lymphocytes (drug effects, immunology, metabolism)
• Tumor Necrosis Factor-alpha (biosynthesis)
• Young Adult