Interleukin (IL)‐21 is a CD4+ T‐cell‐derived cytokine, which is involved in innate and adaptive immune response. In this study, we analysed IL‐21 receptor (IL‐21R) expression in peripheral blood and synovial fluid mononuclear cells, and investigated the role of IL‐21 in the induction of proinflammatory cytokine production by peripheral blood T cells (PB‐T) and synovial fluid T cells (SF‐T) from patients with rheumatoid arthritis (RA). Immunohistochemical staining demonstrated that IL‐21R‐positive cells were significantly increased in inflamed synovial tissues of RA patients compared with osteoarthritis (OA) and healthy controls. Flow cytometric analysis confirmed that IL‐21R was mainly expressed in freshly isolated CD4, CD8, B and NK cells from peripheral blood and synovial fluid, but decreased gradually in T cells 24 h after anti‐CD3 stimulation. PB‐ and SF‐T cells from RA patients were more responsive to IL‐21 when compared with controls. Importantly, isolated PB‐ or SF‐T cells from RA patients, when stimulated with IL‐21 and anti‐CD3 MoAb, secreted markedly higher levels of TNF‐α and IFN‐γ than controls. These data indicate that IL‐21R is overexpressed in the inflamed synovial membrane and in peripheral blood or synovial fluid leukocytes of RA patients, and that IL‐21 enhances local T‐cell activation, proliferation and proinflammatory cytokine secretion. Thus, blockade of IL‐21R signalling pathway may have a therapeutic potential in acute RA patients.

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Aim: Interleukin-1 beta (IL-1β) has been implicated as an extracellular signal in the initiation of apoptosis in neurons and oligodendrocytes after spinal cord injury (SCI). To further characterize the apoptotic cascade initiated by IL-1β after SCI, we examined the expression of IL-1β, p38 mitogen-activated protein kinase (p38 MAPK) and caspase-3 after SCI, and further investigated whether p38 MAPK was involved in neuron apoptosis induced by IL-1β. Methods: Adult rats were given contusion SCI at the T-10 vertebrae level with a weight-drop impactor (10 g weight dropped 25.0 mm). The expression levels of IL-1β, p38 MAPK and caspase-3 after SCI were assessed with Western blots, immunohistochemistry staining, and real time reverse transcription polymerase chain reactions (RT-PCR). Neuron apoptosis was assessed with the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) method. Results: Increased levels of IL-1β and p38 MAPK were observed soon after injury, with a peak in expression levels within 6 h of injury. By 24 h after injury, caspase-3 expression was markedly increased in the injured spinal cord. TUNEL-positive cells were first observed in the lesioned area 6 h after SCI. The largest number of TUNEL-positive cells was observed at 24 h post-SCI. Intrathecal injection of the IL-1 receptor antagonist IL-1Ra significantly reduced expression of p38 MAPK and caspase-3, and reduced the number of TUNEL-positive cells. Moreover, intrathecal injection of an inhibitor of p38 MAPK, SB203580, also significantly reduced the expression of caspase-3, and reduced the number of TUNEL-positive cells in the injured spinal cord. Conclusion: The p38MAPK signaling pathway plays an important role in IL-1β mediated induction of neuron apoptosis following SCI in rats. Key wordsapoptosis; interleukin-1; interleukin-1-receptor antagonist protein; p38 mitogenactivated protein kinase; spinal cord injury; TUNEL

The p75 neurotrophin receptor (p75NTR) is a transmembrane protein that binds nerve growth factor (NGF) and has multiple functions in the nervous system where it is expressed widely during the developmental stages of life, although expression decreases dramatically by adulthood. Expression of p75NTR can increase in pathological states related to neural cell death. p75NTR is a member of the tumour necrosis factor (TNF) receptor family and it consists of intracellular, transmembrane and extracellular domains which are different from other TNF receptors. Either by interacting with tropomyosin receptor kinase (Trk) receptors or via the independent binding of neurotrophin, p75NTR can induce neurite outgrowth and cellular survival or cell apoptosis through several complicated signal transduction pathways. Most of these signalling pathways remain to be elucidated. By interacting with different cellular factors, p75NTR can induce neuron growth cone collapse or regrowth. p75NTR is also expressed in a variety of glial populations. The many functions of p75NTR require further study.

The functional MR imaging signal can be detected in the human cervical spinal cord with functional electrical stimulation. Investigating the FES response in the spinal cord using the spinal fMRI will be helpful for the further discussion on the diagnosis and functional recovery to spinal cord diseases.