Interleukin‐27 enhances the production of tumour necrosis factor‐α and interferon‐γ by bone marrow T lymphocytes in aplastic anaemia

• Published in: British journal of haematology 2011-06, Vol.153 (6), p.764-772
• Main Authors: Li, Jianping, Zhao, Qinjun, Xing, Wen, Feng, Jianming, Wu, Hao, Li, Huiyuan, Ge, Meili, Tian, Kun, Li, Xingxin, Zhou, Jianfeng, Liu, Bin, Zhang, Lei, Zheng, Yizhou, Han, Zhong C.
• Format: Article
• Language: English
• Subjects: Adult; Anemia, Aplastic - immunology; aplastic anaemia; Biological and medical sciences; Bone Marrow Cells - immunology; Case-Control Studies; Cells, Cultured; Cytokine Receptor gp130 - biosynthesis; Cytokine Receptor gp130 - genetics; Female; Hematologic and hematopoietic diseases; Humans; Interferon-gamma - biosynthesis; interferon‐γ; Interleukin-17 - biosynthesis; Interleukin-17 - genetics; Interleukin-17 - immunology; Interleukins - biosynthesis; Interleukins - genetics; interleukin‐27; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Minor Histocompatibility Antigens; Other diseases. Hematologic involvement in other diseases; Receptors, Interleukin - biosynthesis; Receptors, Interleukin - genetics; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - genetics; T-Lymphocytes - immunology; Tumor Necrosis Factor-alpha - biosynthesis; tumour necrosis factor‐α
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/j.1365-2141.2010.08431.x

Summary Aplastic anaemia (AA) is considered as an immune‐mediated bone marrow failure syndrome. The mechanism is involved with a variety of immune molecules including interferon‐γ (IFN‐γ), tumour necrosis factor‐α (TNF‐α) and interleukins (ILs). IL‐27 is a novel member of the IL‐12 family, which mediates T cell response and enhances the production of IFN‐γ. However, little is known about the role of IL‐27 in the development of AA. This study investigated the role of IL‐27 and its receptor IL‐27R in the pathogenesis of AA. Both the mRNA expression of IL‐27/IL‐27R subunits in the bone marrow mononuclear cells (BMMNCs) and the levels of IL‐27 in the marrow plasma in AA were found to be higher than in controls. Increased IL‐27 correlated with the disease severity of AA. Subsequently, we stimulated marrow T lymphocytes with recombinant human (rh)IL‐27 and found that rhIL‐27 enhanced the production of TNF‐α and IFN‐γ in both CD4+ and CD8+ T lymphocytes from AA patients. We also detected increased TNF‐α and IFN‐γ in the supernatants of BMMNCs from AA patients after IL‐27 stimulation. In conclusion, our data suggest that elevated IL‐27 and IL‐27‐induced TNF‐α and IFN‐γ overproduction might be involved in the pathogenesis of AA.