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1.
Kato T Kiire A Yamagata H Yamanaka H Kamatani N 《Modern rheumatology / the Japan Rheumatism Association》2006,16(5):327-329
A 58-year-old Japanese woman with rheumatoid arthritis (RA) suffered from high fever triggered by administration of an influenza
vaccine after a 4-month-long effective treatment course with the TNF-α inhibitor etanercept. Influenza vaccine had been previously
administrated safely to the patient before initiation of etanercept therapy. The fever occurred without other symptoms soon
after vaccine administration, progressed to high fever 1 day later, and spontaneously resolved the second day. The clinical
course appears to be compatible with drug fever closely associated with immediate hypersensitivity (in particular, late-phase
type I allergic reaction), in which T helper (Th) 2 cells play a crucial role. Etanercept can strongly suppress Th1-mediated
reactions; therefore, Th2 activity may be augmented by etanercept treatment in aspect of antagonism between Th1 and Th2 mechanisms.
In RA patients who receive treatment with TNF-α inhibitor such as etanercept, activation of Th2-mediated immune responses
such as immediate hypersensitivity may be a necessary side effect for those who receive vaccinations. 相似文献
2.
《Modern rheumatology / the Japan Rheumatism Association》2013,23(2):183-187
AbstractWe had a rheumatoid arthritis (RA) patient resistant to multiple drugs and who developed panniculitis due to etanercept treatment, then responded fairly well to rituximab. Intracellular staining of cytokines in the peripheral blood mononuclear cells before and after rituximab administration revealed that the cytokine production, representative of T-helper (Th)1-, Th2-, and Th17-type responses, decreased abruptly after the treatment. Interestingly, this timing coincided with that of the manifestation of the beneficial effect. This relationship may provide useful insight into the mechanism of action of the drug and hence about the pathogenesis of RA. 相似文献
3.
《Modern rheumatology / the Japan Rheumatism Association》2013,23(4):372-378
AbstractThis study was performed to analyze the effect of etanercept, the soluble tumor necrosis factor-α (TNF-α) receptor, on the serum levels of several chemokines including monocyte chemotactic protein-1 (MCP-1), regulated upon activation normal T expressed and presumably secreted (RANTES), and granzyme B in rheumatoid arthritis (RA) patients. Twenty-eight patients with RA were administered etanercept once or twice a week for more than 6 months. Clinical and laboratory parameters were measured and serum levels of MCP-1, RANTES, and granzyme B were determined using enzyme-linked immunosorbent assay (ELISA) kits at baseline and at 3 and 6 months after the initial treatment. In addition, the levels of MCP-1, RANTES, and granzyme B produced by cultured synovial cells stimulated with TNF-α were measured. A significant decrease in serum MCP-1 levels was observed at 3 and 6 months after initial treatment with etanercept. Serum RANTES and granzyme B levels did not show significant changes. TNF-α induced MCP-1, RANTES, and granzyme B production in cultured synovial cells from RA patients. Serum MCP-1 levels were significantly correlated with the disease activity scores of 28 joints combined with CRP (DAS28-CRP), indicating the role of MCP-1 in the pathogenesis of rheumatoid inflammation. This study demonstrated that a reduction of MCP-1 production in RA patients was a newly determined effect of etanercept. Another cascade not associated with TNF-α may induce granzyme B and RANTES production in RA patients. 相似文献
4.
《Modern rheumatology / the Japan Rheumatism Association》2013,23(1):15-22
AbstractInterleukin-17 is a proinflammatory cytokine. Recent animal studies have shown that IL-17 plays a role in the initiation and progression of arthritis. However, whether IL-17 has a prominent role in human rheumatoid arthritis (RA) or not remains unclear. Here we investigated the role of IL-17 in patients with RA. cDNA was prepared from knee joint synovial tissues of RA (n = 11) and osteoarthritic (OA, n = 10) patients and PBMC of RA (n = 52) and healthy subjects (n = 34). IL-17 gene expression level was measured by real-time PCR, and was compared with various clinical parameters. IL-17 gene expression in synovial tissues of RA was similar to that in OA. IL-17 gene expression level in PBMC of RA patients was significantly higher than in the control. The response (changes in DAS) to two-week treatment with anti-TNF-α blockers (infliximab or etanercept) did not correlate with changes in IL-17 gene expression levels. The IL-17/TNF-α gene expression ratio at baseline (before treatment) tended to be lower in responders to the treatment. Expression of IL-17 gene in PBMC may be associated with the inflammatory process of RA. IL-17/TNF-α expression ratio is a potentially suitable marker of response to anti-TNF-α therapy. 相似文献
5.
《Modern rheumatology / the Japan Rheumatism Association》2013,23(6):451-458
AbstractApplication of biological agents targeting tumor necrosis factor-α (TNF-α) caused a paradigm shift in the treatment of rheumatoid arthritis (RA). The introduction of infliximab in 2003 and etanercept in 2005 in Japan had a significant impact on both Japanese rheumatologists and RA patients, although serious adverse effects such as bacterial pneumonia, tuberculosis and Pneumocystis jiroveci pneumonia are significant concerns. Based on the data from post-marketing surveillance in Japan and accumulating evidence worldwide, the Internal Medicine Rheumatology Study Group of the Ministry of Health, Labor and Welfare (MHLW), Japan, has updated the guidelines for the use of anti-TNF-α agents for RA, which were subsequently approved by the Board of Japan College of Rheumatology (JCR). In the present revised guidelines, we combined the guidelines for use of each of infliximab and etanercept together with some modifications and precautions, paying special attention to serious adverse reactions. Although it is still controversial whether the use of TNF-α blocking agents per se increases the risk of infection or not, bacterial pneumonia, regardless of the pathogens, is the most frequent complications in RA. The risk factors associated with pneumonia identified in the post-marketing surveillance of infliximab in Japan are presented in this guideline. The diagnostic algorithm is also designed for early diagnosis and treatment of pulmonary lesions seen during the treatment of biological agents. Preventive measures and precautions against tuberculosis, another frequent and significant complication in Japan, are also described. Furthermore, risk factors for developing Pneumocystis pneumonia, which uniquely occurs at 30- to 50-fold frequency under TNF-α blockade therapy in Japan, are described here and its preventive measures are discussed. It is stressed that secondary-care rheumatologists should be better familiarized with the proper use of TNF-α blocking agents and be alert to any adverse events for a better management of RA patients. 相似文献
6.
《Modern rheumatology / the Japan Rheumatism Association》2013,23(4):206-213
AbstractOver a 2-year period, to evaluate the efficacy and safety of biologic agents, etanercept (25?mg twice per week, s.c.) was used to treat 57 rheumatoid arthritis (RA) patients, 9 ankylosing spondylitis (AS) patients, 6 psoriatic arthritis (PSA) patients, and 4 juvenile rheumatoid arthritis (JRA) patients. In addition to inflammatory arthritis, I have used this tumor necrosis factor (TNF) blocker in other rheumatic diseases including idiopathic thrombocytopenic purpura (ITP), Behçet's disease with intractable oral ulcer, fibromyalgia syndrome, and systemic lupus erythematosis with intractable pleural effusion and acute lumbar disc herniation. For RA, after 6 months of etanercept treatment, all the parameters including number of swollen joints, number of tender joints, disease activity score, erythrocyte sedimentation rate, C-reactive protein, and global health status were rapidly improved (P < 0.001 or P < 0.0001). The anticyclic citrullinated peptide (anti-CCP) antibody and rheumatoid factor also significantly declined. For spondyloarthropathy, it also gave a similar effect as to RA. Both Bath Ankylosing Spondylitis Disease Activity Index and Bath Ankylosing Spondylitis Functional Index also improved. One of the two cases with Behçet's disease with intractable oral ulcer had a long-term remission after etanercept. The other Behçet's disease patient with oral ulcer and another with ITP obtained a good response temporarily. The short-term use of etanercept (<3 months) did not bring a significant effect for cases of fibromyalgia syndrome, pleural effusion, and lumbar disc herniation. In conclusion, a dramatic and rapid clinical response in different kinds of arthritis patients can be achieved by etanercept. Moreover, the TNF-α inhibitor also can treat other severe rheumatic-related symptoms. In general, except for a few cases with infection and two cases with malignancy, etanercept was safe in our arthritis patients. We need to study a larger number of patients in order to better understand the efficacy and safety of etanercept. 相似文献
7.
The introduction of tumor necrosis factor (TNF)-α inhibitors s in the late 1990s considerably broadened the treatment options for, and essentially contributed to the successful management of, rheumatoid arthritis (RA) and other immune-mediated inflammatory diseases. Nevertheless, their use during pregnancy is still controversially discussed since it remains unclear whether the benefits of treatment might be outweighed by potential teratogenicity or adverse effects on the course of pregnancy. In this case series report we describe the course and outcome of eight pregnancies in five women (four with RA and one with ankylosing spondylitis) at our private clinical practice treated with the TNF-α inhibitor etanercept at the time of conception and during pregnancy. The course was inconspicuous in six of the eight pregnancies; in one case a megacolon congenitum was diagnosed 2 weeks after birth, while one spontaneous abortion occurred in the 10th week of pregnancy after a disease flare following treatment discontinuation with etanercept in the 5th week of pregnancy. Based on our experience to date and the currently available literature data, we believe that continuation of treatment with TNF-α blockers is justified in pregnant patients with otherwise high disease activity and disease progression. 相似文献
8.
Katja Perdan-Pirkmajer Alojzija Hočevar Žiga Rotar Janez Žibert Vera Ferlan Marolt Filip Gučev Matija Tomšič 《Rheumatology international》2013,33(11):2885-2888
Tumour necrosis factor-alpha (TNF-α) inhibitors are widely used in the management of patients with rheumatoid arthritis (RA) and spondylarthritides. However, TNF-α inhibition may lead to adverse events, including liver injury. The RA patients are frequently treated with several potentially hepatotoxic drugs concomitantly; hence, a causative link between TNF-α inhibitors and liver injury is usually difficult to establish. We report two cases of RA patients who developed histologically manifest liver injury shortly after the introduction of treatment with two different TNF-α inhibitors. Furthermore, we present the analysis of the laboratory data from the BioRx.si registry (the Slovenian national registry of rheumatologic patients treated with biologicals) and provide evidence that elevated levels of serum aminotransferase can be observed in patients treated with TNF-α inhibitors. Additionally, our analysis suggests no significant differences between the impact of adalimumab and etanercept on aminotransferase levels. Although the use of TNF-alpha inhibitors is safe and efficient, we suggest that continuous careful monitoring of aminotransferase levels in patients treated with these agents is probably warranted. 相似文献
9.
Chou CT 《Modern rheumatology / the Japan Rheumatism Association》2006,16(4):206-213
Over a 2-year period, to evaluate the efficacy and safety of biologic agents, etanercept (25?mg twice per week, s.c.) was used to treat 57 rheumatoid arthritis (RA) patients, 9 ankylosing spondylitis (AS) patients, 6 psoriatic arthritis (PSA) patients, and 4 juvenile rheumatoid arthritis (JRA) patients. In addition to inflammatory arthritis, I have used this tumor necrosis factor (TNF) blocker in other rheumatic diseases including idiopathic thrombocytopenic purpura (ITP), Behçet's disease with intractable oral ulcer, fibromyalgia syndrome, and systemic lupus erythematosis with intractable pleural effusion and acute lumbar disc herniation. For RA, after 6 months of etanercept treatment, all the parameters including number of swollen joints, number of tender joints, disease activity score, erythrocyte sedimentation rate, C-reactive protein, and global health status were rapidly improved (P < 0.001 or P < 0.0001). The anticyclic citrullinated peptide (anti-CCP) antibody and rheumatoid factor also significantly declined. For spondyloarthropathy, it also gave a similar effect as to RA. Both Bath Ankylosing Spondylitis Disease Activity Index and Bath Ankylosing Spondylitis Functional Index also improved. One of the two cases with Behçet's disease with intractable oral ulcer had a long-term remission after etanercept. The other Behçet's disease patient with oral ulcer and another with ITP obtained a good response temporarily. The short-term use of etanercept (<3 months) did not bring a significant effect for cases of fibromyalgia syndrome, pleural effusion, and lumbar disc herniation. In conclusion, a dramatic and rapid clinical response in different kinds of arthritis patients can be achieved by etanercept. Moreover, the TNF-α inhibitor also can treat other severe rheumatic-related symptoms. In general, except for a few cases with infection and two cases with malignancy, etanercept was safe in our arthritis patients. We need to study a larger number of patients in order to better understand the efficacy and safety of etanercept. 相似文献
10.
目的探讨甲泼尼龙对难治性强直性脊柱炎(ankylosing spondylitis,AS)患者外周血T辅助(Thelper,Th)细胞活化状态及其细胞因子分泌的影响。方法用三色流式细胞分析法对AS患者治疗前后和正常对照组外周血淋巴细胞胞内细胞因子(IFN-γ、TNF-α及IL-4)和Th1、Th2细胞进行分析,同时采用夹心酶联免疫吸附法测定血清IFN-γ、TNF-α及IL-4水平,分析其与临床疗效指标的相关性。结果难治性AS患者外周血Th1细胞百分率及血清IFN-γ,TNF-α水平高于正常对照组(P〈0.05),与BASDAI、BASFI、BASMI评分、夜间痛、血沉和C反应蛋白呈正相关(P〈0.05);Th2细胞百分率及血清IL-4低于正常对照组(P〉0.05),与以上疗效评价指标呈负相关(P〈0.05)。甲泼尼龙治疗后Th1细胞百分率及血清IFN-γ、TNF-α水平较治疗前明显降低,Th2细胞百分率和血清IL-4较治疗前升高。结论难治性AS患者外周血淋巴细胞存在Th1和Th2细胞平衡偏移,Th1细胞占优势。甲泼尼龙治疗可下调Th1细胞功能,抑制促炎因子IFN-γ、TNF-α分泌,并能显著改善AS患者的关节症状和疾病活动性。 相似文献
11.
Keystone EC 《The Journal of rheumatology》2011,38(8):1552-1562
Given the important role tumor necrosis factor-α (TNF-α) antagonists play in managing rheumatoid arthritis and the concern for safety during longterm therapy, we reviewed the latest evidence regarding longterm risk of infection and malignancy with TNF-α antagonists. Our objective was to provide clinicians with information that can be used to counsel and monitor patients who may be candidates for biologic therapy for rheumatoid arthritis (RA). Risk is examined in the context of background infection and malignancy rates in RA. Randomized controlled trial (RCT) data and observational studies summarizing the risk of infection and/or malignancy in RA and specific risks associated with the use of anti-TNF-α biologic agents (adalimumab, infliximab, and etanercept) were identified through a PubMed search. Overall, patients with RA appear to have an approximately 2-fold increased risk of serious infection compared to the general population and non-RA controls, irrespective of TNF-α antagonist use. Although data on infection rates with TNF-α antagonist use are contradictory, caution is merited. Recent analyses suggest that the risk of infection is highest within the first year. Regarding malignancy risk, RCT and observational data are also conflicting; how ever, caution is warranted regarding lymphoproliferative cancers in children and adolescents. 相似文献
12.
Yumi Motoki Kenji Tani Teruki Shimizu Hiroyuki Tamiya Kayoko Hase Yasukazu Ohmoto Kouji Matsushima Saburo Sone 《Modern rheumatology / the Japan Rheumatism Association》2003,13(2):114-120
CXC chemokine receptor 3 (CXCR3) is selectively expressed on T helper 1 (Th1) type T cells and has been shown to be responsible
for Th1-dominant immune responses. In this study, we analyzed the expression of CXCR3 on peripheral blood T lymphocytes of
patients with rheumatoid arthritis (RA) by FACS analysis using antihuman CXCR3 monoclonal antibody and determined the clinical
relevance in this disease. Significantly higher expression of CXCR3 was found on peripheral blood CD4+ T lymphocytes of RA
patients than healthy controls. The CXCR3 expression in RA patients with a high erythrocyte sedimentation rate was significantly
higher than in those with a low erythrocyte sedimentation rate. Moreover, we found that the CXCR3 expression in RA patients
with long-term disease duration was significantly higher than in those with short-term disease. On the other hand, CC chemokine
receptor 4 (CCR4), which was shown to be selectively expressed on Th2-type T cells, was expressed at low levels in RA patients
as well as in healthy controls. The serum level of interleukin (IL)-18 in RA patients was higher than that in healthy controls,
although there was no statistically significant difference. This study suggests that the Th1 immune response is predominant
in RA and that CXCR3 may have relevance in regard to the disease course in RA patients.
Received: January 28, 2002 / Accepted: August 14, 2002 相似文献
13.
Double-negative T cells regulate the progression of liver fibrosis through Th9 cells differentiation
Chenyang Han Hongyan Pei Yongjia Sheng Jin Wang Xiaohong Zhou Wenyan Li Shasha Wu Yi Yang Jian Sheng Chenxi Cao 《Liver international》2023,43(7):1604-1613
Our previous study found that double negative T cells (DNTs) could promote the NLRP3 activation through high expression of TNF-α, thereby leading to hepatic fibrosis progression. We focused on investigating the role and mechanism of DNTs in regulating the Th9 cells differentiation in liver fibrosis. In our results, among patients with liver fibrosis, the proportions of peripheral blood DNTs and Th9 cells were up-regulated and positively correlated. While promoting the progression of liver fibrosis in mice, DNTs could elevate the proportion of Th9 cells and activate the TNFR2-STAT5-NF-κB pathway. The use of IL-9 and TNF-α monoclonal antibodies (mAbs) inhibited the effect of DNTs and lowered the proportion of Th9 cells in tissues. In vitro experiments showed that DNTs could promote the Th9 cells differentiation of Naive T cells, while TNF-α mAbs could inhibit such effect of DNTs to lower the proportion of Th9 cells. We found that DNTs can activate TNFR2-STAT5-NF-κB pathway by secreting TNF-α, thereby promoting the Th9 Cells differentiation to facilitate the progression of liver fibrosis. There is interaction between DNTs and Th9 cells. 相似文献
14.
Hiroshi Matsumoto Hideki Koga Mitsuo Iida Ken-Ichi Tarumi Minoru Fujita Ken Haruma 《Scandinavian journal of gastroenterology》2013,48(11):1320-1329
Objective. Tumor necrosis factor (TNF)-α-converting enzyme (TACE), which has been purified, regulates maturity of TNF-α. Matrix metalloproteinases (MMPs) play a key role in various inflammatory conditions. The incidence of intestinal damage has increased, but the mechanism and treatment have not been well understood. The purpose of this study was to investigate the roles of TACE and MMP in indomethacin (Indo)-induced intestinal damage as well as the therapeutic effects of TACE inhibitor and selective MMP inhibitor (sMMPi) on this intestinal damage in rats.Material and methods. In the first experiment, serial changes in intestinal ulcers and the production of MMP were investigated. In the second experiment, we assessed the effect of three TACE and/or MMP inhibitors and the production of TNF-α, TACE, MMP-3, -9 and tissue inhibitor of MMP (TIMP)-1. The rats were divided into five groups: a control group, and four groups that received Indo alone, Indo plus TACE inhibitor (GM6001), Indo plus a selective MMP-3 inhibitor and Indo plus an MMP-9/13 inhibitor, respectively.Results. MMP-3 was overexpressed at 24?h after Indo administration, when intestinal injury was most prominent macroscopically and microscopically. GM6001 significantly decreased ulcer severity and suppressed MMP-3 in a dose-dependent fashion. The selective MMP-3 inhibitor dose-dependently ameliorated intestinal damage to the same degree as GM6001, but the MMP-9 inhibitor had no effect on the injury.Conclusions. MMP-3 inhibition ameliorates intestinal damage without apparently affecting either TNF-α or TACE production and the dose–response curve suggests that the beneficial effect of the so-called TACE inhibitor is actually mainly mediated via MMP-3 inhibition rather than TNF-α inhibition. 相似文献
15.
Lane MA McDonald JR Zeringue AL Caplan L Curtis JR Ranganathan P Eisen SA 《Medicine》2011,90(2):139-145
Medications used to treat rheumatoid arthritis (RA) may confer an increased risk of infection. We conducted a retrospective cohort study of veterans with RA followed in the United States Department of Veterans Affairs health care system from October 1998 through September 2005. Risk of hospitalization for infection associated with tumor necrosis factor (TNF)-α antagonists therapy was measured using an extension of Cox proportional hazards regression, adjusting for demographic characteristics, comorbid illnesses, and other medications used to treat RA. A total of 20,814 patients met inclusion criteria, including 3796 patients who received infliximab, etanercept, or adalimumab. Among the study cohort, 1465 patients (7.0%) were hospitalized at least once for infection. There were 1889 hospitalizations for infection. The most common hospitalized infections were pneumonia, bronchitis, and cellulitis. Age and several comorbid medical conditions were associated with hospitalization for infection. Prednisone (hazard ratio [HR], 2.14; 95% confidence interval [CI], 1.88-2.43) and TNF-α antagonist use (HR, 1.24; 95% CI, 1.02-1.50) were associated with hospitalization for infection, while the use of disease-modifying antirheumatic drugs (DMARDs) other than TNF-α antagonists was not. Compared to etanercept, infliximab was associated with risk for hospitalization for infection (HR, 1.51; 95% CI, 1.14-2.00), while adalimumab use was not (HR, 0.95; 95% CI, 0.68-1.33). In all treatment groups, rate of hospitalization for infection was highest in the first 8 months of therapy. We conclude that patients with RA who are treated with TNF-α antagonists are at higher risk for hospitalization for infection than those treated with other DMARDs. Prednisone use is also a risk factor for hospitalization for infection. 相似文献
16.
17.
肿瘤坏死因子-α拮抗剂治疗中国汉族人群强直性脊柱炎369例不良反应初步研究 总被引:1,自引:0,他引:1
目的 旨在评价接受了肿瘤坏死因子(TNF)-α拮抗剂治疗的中国汉族人群强直性脊柱炎(AS)患者的不良反应,为生物制剂的临床治疗提供参考依据.方法 本研究纳入在我科接受了TNF-α拮抗剂治疗的369例中国汉族人群AS患者,未完全跟踪随访给药1011次.所有患者均评估了用药后2h出现的不良反应,对其中126例长期用药患者进行了第8、12、52、104周的随访.观察患者用药后2h的短期不良反应和长期不良反应.采用Fisher确切概率法进行统计分析.结果 接受TNF-α拮抗剂治疗的369例AS患者,随访用药后2h共计发生30次不良反应.英夫利西单抗和重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(rhTNFR:Fc)引起的短期不良反应发生率差异无统计学意义(分别为3.8%,2.6%,P=0.31).126例患者分别依次进行了第8、12、52、104周的随访,共计39例发生不良反应,长期应用英夫利西单抗和rhTNFR:Fc不良反应发生率差异无统计学意义(分别为49%,51%,P=0.69).结论 中国汉族人群AS患者在接受TNF-α拮抗剂治疗时应注意上述不良反应的发生,尤其应注意第3、4次接受英夫利西单抗治疗患者的不良反应.接受英夫利西单抗和rhTN FR:Fc治疗的患者用药后2h内和长期(≥2年)治疗的不良反应发生相当. 相似文献
18.
Akinori Yamamoto Kojiro Sato Fumihiko Miyoshi Yasufumi Shindo Yoshihiro Yoshida Kazuhiro Yokota Kyoichi Nakajima Haruhiko Akiba Yu Asanuma Yuji Akiyama Toshihide Mimura 《Modern rheumatology / the Japan Rheumatism Association》2010,20(2):183-187
We had a rheumatoid arthritis (RA) patient resistant to multiple drugs and who developed panniculitis due to etanercept treatment, then responded fairly well to rituximab. Intracellular staining of cytokines in the peripheral blood mononuclear cells before and after rituximab administration revealed that the cytokine production, representative of T-helper (Th)1-, Th2-, and Th17-type responses, decreased abruptly after the treatment. Interestingly, this timing coincided with that of the manifestation of the beneficial effect. This relationship may provide useful insight into the mechanism of action of the drug and hence about the pathogenesis of RA. 相似文献
19.
Yong-Mei Guo Makoto Hirokawa Naoto Takahashi Masumi Fujishima Naohito Fujishima Atsushi Komatsuda Hiroyuki Tagawa Hideaki Ohyagi Yoshihiro Michishita Kumi Ubukawa Miwa Hebiguchi Weiguo Xiao Kenichi Sawada 《International journal of hematology》2010,91(1):61-68
We have developed a method that cells exhibiting typical dendritic cell (DC) characteristics are generated from human CD34+ cells and phagocytose cogenerating erythroid progenitor cells in the presence of tumor necrosis factor-α (TNF-α), interleukin-3, stem cell factor and erythropoietin. Using this system, we titrated the effects of TNF antagonists, etanercept and infliximab, on TNF-α activity. We found that 1 μg/ml etanercept dramatically inhibited the generation of CD11c+ cells accompanying with a complete recovery of the generation of erythroid progenitors. Infliximab at 200 μg/ml exhibited a similar effect to that observed for etanercept. The delayed addition of etanercept to this culture system at day five resulted in significant inhibitory effects on the generation of CD11c+, CD4+ and CD86+ cells. These results indicate that TNF antagonists administered at a concentration that is achievable in vivo, neutralize the biologic effects of TNF-α in generating CD11c+ cells and that a delay in the administration of these antagonists for as long as 5 days partially inhibits the biologic activity of TNF-α. These findings may contribute to a great understanding of anti-TNF therapy in patients with an overproduction of cytokines such as hemophagocytic syndromes. 相似文献
20.
《The Egyptian Rheumatologist》2020,42(3):177-181
BackgroundIncreased coronary artery atherosclerosis in rheumatoid arthritis (RA) may cause significant mortality. Tumor necrosis factor (TNF) is a potent proinflammatory cytokine that has been involved in RA pathogenesis and atherosclerosis.Aim of the workTo determine the association between TNF-α rs1800629 polymorphism and carotid atherosclerosis in RA patients.Patients and methodsThis study was carried out on 50 RA patients and 40 age and sex matched healthy control. All patients were subjected to full history taking, thorough clinical examination, and assessment of disease activity score (DAS28). Carotid artery intima–media thickness (IMT) was measured by Doppler ultrasonography. TNF-α −308A/G (rs1800629) polymorphism was assessed.ResultsThe mean age of patients was 41.2 ± 13.2 years with disease duration of 6.1 ± 4.5 years. The mean DAS28 was 4.1 ± 0.8 and Larsen score 2.1 ± 0.9. The mean IMT was significantly higher in patients (0.78 ± 0.47 mm) compared to the control (0.44 ± 0.16 mm) (p < 0.001). Carotid plaques and calcifications were present in 2 and 3 patients respectively. Regarding the TNF-α polymorphism, there was a significantly higher frequency of GG (60%) followed by GA (24%) and AA (16%) (p < 0.0001). All control had GG genotype except 1 patient had GA. The G allele was significantly increased (72%) compared to the A allele (28%) (p < 0.0001). The mean carotid IMT was significantly higher in AA genotype (1.2 ± 0.4 mm) compared to GA (1.02 ± 0.5 mm) and GG (0.5 ± 0.3 mm) (p < 0.001).ConclusionRheumatoid arthritis and atherosclerosis are strictly linked to each other; TNF-α −308A/G polymorphism might increase atherosclerotic susceptibility in RA patients through increased risk of inflammation with subsequent abnormal lipid profile. 相似文献