IL-17-producing Th (Th17) comprise a distinct lineage of pro-inflammatory Th that are major contributors to autoimmune diseases. Treatment with IL-6 and transforming growth factor beta (TGFbeta) induces naive CD4+ T cells to generate Th17, which also requires expression of the IL-6/TGFbeta target RORgammat. We reported that IL-6 transduces two signaling pathways via tyrosine redidues of the signal transducer gp130: one depends on signal transducers and activators of transcription (STAT)-3 activation and the other on Src homology region 2 domain-containing phosphatase 2 (SHP2)/Grb2 associated binder (Gab)/mitogen-activated protein kinase (MAPK) activation. Here, we showed that CD4+ T cells carrying a mutant gp130 that transduces the SHP2/Gab/MAPK pathway but not the STAT3-mediated one failed to develop into Th17, while CD4+ T cells whose mutant gp130 transduces the STAT3 signal only generated Th17, indicating that IL-6 acts directly on T cells through the tyrosine residues of gp130 required for STAT3 activation to promote the development of Th17. Moreover, we found that gp130-STAT3 pathway is essential for Th17 development and for the expression of RORgammat by using T cells specifically lacking gp130 and STAT3. Noteworthy is that the regulatory T cell (Treg) percentages and numbers were comparable between all mutant mice we tested in vivo, although we showed that IL-6-gp130-STAT3 pathway suppressed Treg development in vitro. Thus, we conclude that IL-6 acts directly to promote the development of Th17 by activating the T cell gp130-STAT3 pathway but has a minimum effect on Treg development at least in the steady state in vivo. Therefore, blockade of IL-6-gp130-STAT3 pathway in CD4+ T cells could be a good target for controlling unwanted Th17-mediated immune responses including autoimmune diseases.

Object Neurological deterioration due to spinal epidural hematoma (SEH) is a rare but significant complication of spinal surgery. The frequency of hematoma evacuation after spinal surgery is reportedly 0.1%–3%. The objective of this study was to investigate the symptomatology of SEH and the frequency of evacuation for each surgical procedure after spinal decompression surgery. Methods This is a retrospective study of 26 patients who underwent SEH evacuation after spinal decompression surgery between 1986 and 2005. During this period, 6356 spinal decompression surgeries were performed. The factors studied were the frequency of SEH evacuation for each surgical procedure, symptoms, time to SEH evacuation, comorbidities, and neurological recovery. Results The frequency of SEH evacuation was 0.41% (26 of 6356) for all operations. The frequency for each surgical procedure was 0% (0 of 1568) in standard lumbar discectomy, 0.50% (8 of 1614) in lumbar laminectomy, 0.67% (8 of 1191) in posterior lumbar interbody fusion, 4.46% (5 of 112) in thoracic laminectomy, 0.44% (4 of 910) in cervical laminoplasty, and 0.21% (1 of 466) in cervical anterior spinal fusion. Nine patients had comorbidities involving hemorrhage. Spinal epidural hematoma evacuation was performed between 4 hours and 8 days after the initial operation. Whereas severe paralysis was observed within 24 hours in most patients undergoing cervical and/or thoracic surgery, half of the patients undergoing lumbar surgery had symptoms of SEH such as leg pain or bladder dysfunction after suction drain removal. The shorter the period to evacuation, the better were the results of neurological recovery. Conclusions Postoperative SEH was most frequent after thoracic laminectomy. In cervical and thoracic surgeries, symptoms of SEH were noted within 24 hours, mostly severe paralysis, and almost half of the lumbar surgery patients had symptoms after suction drain removal.

Objective. To determine whether apoptosis occurs in rheumatoid arthritis (RA) synoviocytes, and if this phenomenon is dependent on the Fas/Apo‐1 pathway. Methods. Apoptotic change in vivo was examined in RA synovial cells by several standard methods. The ability of cells to undergo Fas‐induced apoptosis was determined in vitro. Results. Typical apoptotic change was demonstrated in RA synovial cells by each method. Anti‐Fas antibody induced apoptotic synovial cell death in vitro. Conclusion. This is the first reported study to demonstrate apoptosis in RA synovial cells. The findings indicate that rheumatoid synoviocytes undergo Fas‐mediated apoptosis.

1) There was no correlation between radiologic degeneration of cranial adjacent segment and clinical results. 2) Risk factors for postoperative radiologic degeneration could not be detected in terms of each preoperative radiologic factor. 3) Coexistence of horizontalization of the lamina at L3 and facet tropism at L3-L4 may be one of the risk factors for neurologic deterioration resulting from accelerated L3-L4 degenerative change after L4-L5 PLIF.

Objective. To examine whether nuclear factor κB (NF‐κB) is activated in cultured synovial cells in response to tumor necrosis factor α (TNFα) and to investigate the correlation between NF‐κB activation and synovial cell proliferation. Methods. Activation of NF‐κB was detected by electrophoretic mobility shift assay. The transcription of several NF‐κB–dependent genes was evaluated by reverse transcriptase polymerase chain reaction and transient expression assay using human immunodeficiency virus–long terminal repeat chloramphenicol acetyltransferase. Proliferative activity was determined by measurement of 3H‐thymidine incorporation. Results. Stimulation of synovial cells with TNFα activated NF‐κB and subsequent transcription of several genes. Treatment of synovial cells with N‐acetyl‐L‐cysteine (NAC), an antioxidant agent, inhibited TNFα‐induced NF‐κB activation and transcription. Moreover, NAC also inhibited synovial cell proliferation induced by TNFα. Conclusion. Our results suggest that NF‐κB plays a pivotal role in synovial cell activation by TNFα. Thus, suppression of NF‐κB could be a potential therapeutic modality for synovitis such as that of rheumatoid arthritis.