共查询到20条相似文献,搜索用时 15 毫秒
1.
A J Schuerwegh L S De Clerck L De Schutter C H Bridts A Verbruggen W J Stevens 《Cytokine》1999,11(10):783-788
Type 1 cytokines (a.o. IL-2 and IFN-gamma) play an important role in the pathogenesis of rheumatoid arthritis. On the other hand, IgE-mediated diseases such as allergic asthma and atopic dermatitis show a type 2 cytokine (amongst others IL-4 and IL-5) profile.This study examined simultaneously the intracellular production of IL-2, IFN-gamma, IL-4 and IL-5 in T-lymphocytes of patients with rheumatoid arthritis during treatment with methotrexate or salazopyrin, patients with allergic asthma or atopic dermatitis under stable treatment, compared to healthy controls.A three-colour flow cytometric analysis was used for cytokine detection in T-helper cells and T-suppressor/cytotoxic cells.Compared to controls, patients with symptomatic atopic dermatitis showed an increased number of IL-4-producing T-helper lymphocytes in basal circumstances (P=0.001), in contrast to asymptomatic allergic asthma patients. Compared to controls, rheumatoid arthritis patients, treated with salazopyrin, showed an increased number of IL-2-producing T-helper and T-suppressor/cytotoxic lymphocytes after in vitro stimulation with PMA and ionomycin (P=0.01). In contrast, rheumatoid arthritis patients, treated with methotrexate, a more potent disease modifying drug, did not show this type 1 cytokine profile. A positive correlation was found between the number of IFN-gamma producing T-helper cells and disease activity (Ritchie Index and number of swollen joints) in both rheumatoid arthritis patient groups.Active atopic dermatitis patients showed a type 2 cytokine profile, whereas stable asthma patients with lower disease activity did not show a predominance of type 2 cytokines. Rheumatoid arthritis patients under treatment with salazopyrin had a type 1 cytokine profile, which could not be demonstrated in patients treated with methotrexate. This imbalance between type 1 and type 2 cytokines in different immune mediated disorders can be related with treatment and the grade of disease activity. These results stress the need for further investigation of the influence of therapy on cytokine profiles. 相似文献
2.
Parvovirus (PV) B19 is the causative agent of the childhood disease erythema infectiosum. An association of PV B19 with chronic
arthropathies, sometimes resembling rheumatoid arthritis or juvenile idiopathic arthritis (JIA), has repeatedly been described.
Other studies, however, have failed to identify any such relationship. In order to study further whether there is a link between
PV B19 and JIA, we determined the prevalence of PV B19 specific IgG antibodies in serum samples from children with rheumatoid
diseases and compared it with the prevalence in unaffected children We reasoned that if there is an association between PV
B19 and JIA, then the prevalence of PV B19 IgG in the children with JIA should be higher than in the control group. PV B19
IgG status was tested in 406 children with JIA and related diseases, and in 146 children constituting a control group. The
percentage of PV B19 IgG positive children was not significantly elevated in the disease subgroups compared with age-matched
control groups. In conclusion, our findings do not support the hypothesis that human parvovirus B19 is involved in the pathogenesis
of JIA. 相似文献
3.
A number of clinical trials have been done to investigate the role of interleukin-6 (IL-6) as a potential therapeutic target in rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA). Most of the data testing this comes from trials of the humanized anti Il-6 receptor antibody tocilizumab. Results from clinical trials worldwide have been promising so far. Additional study will define the ultimate role of tocilizumab and Il6 inhibitors in the treatment paradigms for RA and JIA. 相似文献
4.
Therapeutic monoclonal antibodies have revolutionized the treatment of various inflammatory diseases. Immunogenicity against
these antibodies has been shown to be clinically important: it is associated with shorter response duration because of diminishing
concentrations in the blood and with infusion reactions. Concomitant immunomodulators in the form of methotrexate or azathioprine
reduced the immunogenicity of therapeutic antibodies in rheumatoid arthritis, Crohn disease, and juvenile idiopathic arthritis.
The occurrence of adverse events does not increase when immunomodulators are added to therapeutic antibodies. The mechanism
whereby methotrexate and azathioprine influence immunogenicity remains unclear. Evidence-based consensus on prescribing concomitant
immunomodulators is needed. 相似文献
5.
The availability of agents that block the biological activity of tumor necrosis factor α (TNFα) in rheumatoid arthritis (RA)
has permitted studies that confirm the key role of this cytokine in the pathogenesis of this disease. To date, two anti-TNF
agents, infliximab and etanercept, have been approved for use in treatment. Clinical trials of these agents demonstrate efficacy
for the control of symptoms and signs and acceptable safety in patients who have failed to respond adequately to conventional
therapy. Combination with methotrexate appears to be particularly effective and may provide the main initial indication for
clinical application in the first instance. Repeated administration of anti-TNF therapies over a one year period results in
sustained reduction in symptoms and signs of RA in the majority of patients. It has recently become apparent that anti-TNF
therapy protects joints from structural damage. These findings imply that TNFα has a critical role in the bone and cartilage
damage associated with RA.
Evidence to date support the hypothesis that there are 2 particularly important mechanisms of action; deactivation of the
proinflammatory cytokine cascade at the site of inflammation and diminished recruitment of inflammatory cells from blood to
the rheumatoid joint. 相似文献
6.
Lazaro E. Aira Patricia Hernández Dinorah Prada Araceli Chico Jorge A. Gómez Zuyén González 《MABS-AUSTIN》2016,8(1):187-195
Rheumatoid arthritis is an autoimmune disease characterized by joint inflammation that affects approximately 1% of the general population. Itolizumab, a monoclonal antibody specific for the human CD6 molecule mainly expressed on T lymphocytes, has been shown to inhibit proliferation of T cells and proinflammatory cytokine production in psoriasis patients. We have now assessed the immunological effect of itolizumab in combination with methotrexate in rheumatoid arthritis by analyzing clinical samples taken from 30 patients enrolled in a clinical trial. T and B cell subpopulations were measured at different time points of the study. Plasma cytokine levels and anti-idiotypic antibody response to itolizumab were also evaluated. The combined treatment of itolizumab and methotrexate led to a reduction in the frequency of T cell subpopulations, and plasma levels of proinflammatory cytokines showed a significant decrease up to at least 12 weeks after treatment ended. No anti-idiotypic antibody response was detected. These results support the relevance of the CD6 molecule as a therapeutic target for the treatment of this disease. 相似文献
7.
Anti-interleukin-6 receptor antibody, tocilizumab, for the treatment of autoimmune diseases 总被引:1,自引:0,他引:1
Interleukin (IL)-6 is a cytokine with multiple biological activities. It contributes to host defense against pathogens, whereas accelerated production of IL-6 plays a significant pathological role in various diseases. Clinical trials have demonstrated the efficacy of tocilizumab, a humanized anti-IL-6 receptor antibody, for patients with rheumatoid arthritis, Castleman's disease or juvenile idiopathic arthritis, leading to approval of this innovative drug for the treatment of these diseases. Since IL-6 has been demonstrated to play a significant role in the development of various other autoimmune and inflammatory diseases, tocilizumab can be expected to become a novel drug for such diseases as well. 相似文献
8.
Complementary and alternative medicine products are increasingly being used for the treatment of autoimmune diseases. However,
the mechanisms of action of these agents are not fully defined. Using the rat adjuvant arthritis (AA) model of human rheumatoid
arthritis, we determined whether the ethanol extract of Celastrus aculeatus Merr. (Celastrus), a Chinese herb, can down-modulate the severity of AA, and also examined the Celastrus-induced changes
in immune responses to the disease-related antigen mycobacterial heat-shock protein 65 (Bhsp65). AA was induced in the Lewis
(LEW; RT.1l) rat by immunization subcutaneously with heat-killed M. tuberculosis H37Ra (Mtb). Celastrus was fed to LEW rats by gavage daily, beginning either before Mtb challenge (preventive regimen) or
after the onset of AA (therapeutic regimen). An additional group of rats was given methotrexate for comparison. All rats were
graded regularly for the signs of arthritis. In parallel, the draining lymph node cells of Celastrus-treated rats were tested
for proliferative and cytokine responses, whereas their sera were tested for the inflammatory mediator nitric oxide. Celastrus
feeding suppressed both the induction as well as the progression of AA, and the latter effect was comparable to that of methotrexate.
Celastrus treatment induced relative deviation of the cytokine response to anti-inflammatory type and enhanced the production
of anti-Bhsp65 antibodies, which are known to be protective against AA. Celastrus feeding also reduced the levels of nitric
oxide. On the basis of our results, we suggest further systematic exploration of Celastrus as an adjunct therapeutic modality
for rheumatoid arthritis. 相似文献
9.
Woo P Wilkinson N Prieur AM Southwood T Leone V Livermore P Wythe H Thomson D Kishimoto T 《Arthritis research & therapy》2005,7(6):R1281-R1288
Eighteen Caucasian (white, Middle East and Asian) children diagnosed by paediatric rheumatologists in the UK and France as
having systemic juvenile idiopathic arthritis (sJIA) were enrolled in this open label, single dose trial. All patients had
evidence of continued symptoms and disease activity for at least three months while receiving >0.2 mg/kg/day of prednisolone,
or its equivalent, prior to recruitment. Twelve patients also received methotrexate (≤20 mg/m2/week). The patients were divided into three groups receiving 2, 4 or 8 mg/kg of MRA (tocilizumab) by intravenous infusion.
No evidence of dose-limiting toxicity was observed and there were no dose-limiting safety issues. MRA appeared to be dramatically
effective, with clinical and laboratory responses observed by 48 h post infusion, and these improvements continued well after
serum MRA was undetectable. Eleven patients achieved the JIA definition of improvement (at least 3 of 6 core set criteria
with a 30% improvement and no more than one worsened by 30%) and eight achieved ≥50% improvement. There were no observable
differences with age. Clinical improvement in these children was observed for up to eight weeks, supporting the hypothesis
that IL-6 is a key cytokine in the upregulation of genes crucial in the inflammation processes of sJIA, and the possibility
of sequestration of MRA in the extra-vascular compartment needs to be considered. 相似文献
10.
Tabarkiewicz J Postępski J Olesińska E Roliński J Tuszkiewicz-Misztal E 《Folia histochemica et cytobiologica / Polish Academy of Sciences, Polish Histochemical and Cytochemical Society》2011,49(1):188-199
Childhood chronic arthritis of unknown etiology is known collectively as juvenile idiopathic arthritis (JIA) and consists of heterogeneous subtypes with unique clinical patterns of disease. JIA is the commonest rheumatic disease in children and may still result in significant disability, with joint deformity, growth impairment, and persistence of active arthritis into adulthood. Basic research is rather focused on rheumatoid arthritis, and this lead to small number of publications considering JIA. In this study we examine, by flow cytometry, the expression of dendritic cells (DCs) in the peripheral blood and synovial fluid of children with active JIA in a group of 220 patients. We reveal a significant decrease in the percentage of immature DCs in the blood of patients compared to control children. Surprisingly, we found higher percentages of mature circulating dendritic cells. Both populations of DCs, immature and mature, were accumulated in patients' synovial fluid. We also confirmed the presence of CD206+/CD209+ in JIA samples, which can represent a population of macrophages with dendritic cells morphology. Our results support the thesis that dendritic cells are crucial in the induction and maintenance of autoimmune response and local inflammation during juvenile idiopathic arthritis. 相似文献
11.
12.
Maja Bulatovi? ?alasan Oscar FC van den Bosch Marjonne CW Creemers Martijn Custers Antonius HM Heurkens Jan Maarten van Woerkom Nico M Wulffraat 《Arthritis research & therapy》2013,15(6):R217
Introduction
The aim of this study was to determine the prevalence of gastrointestinal and behavioural symptoms occurring before (anticipatory/associative) and after methotrexate (MTX) administration, termed MTX intolerance, in rheumatoid (RA) and psoriatic arthritis (PsA).Methods
Methotrexate Intolerance Severity Score (MISS), previously validated in juvenile idiopathic arthritis patients, was used to determine MTX intolerance prevalence in 291 RA/PsA patients. The MISS consisted of four domains: abdominal pain, nausea, vomiting and behavioural symptoms, occurring upon, prior to (anticipatory) and when thinking of MTX (associative). MTX intolerance was defined as ≥6 on the MISS with ≥1 point on anticipatory and/or associative and/or behavioural items.Results
A total of 123 patients (42.3%) experienced at least one gastrointestinal adverse effect. The prevalence of MTX intolerance was 11%. MTX intolerance prevalence was higher in patients on parenteral (20.6%) than on oral MTX (6.2%) (p < 0.001).Conclusion
Besides well-known gastrointestinal symptoms after MTX, RA and PsA patients experienced these symptoms also before MTX intake. RA and PsA patients on MTX should be closely monitored with the MISS for early detection of MTX intolerance, in order to intervene timely and avoid discontinuation of an effective treatment. 相似文献13.
Progress into the understanding of immunopathology in rheumatoid arthritis is reviewed in the present article with regard
to pro-inflammatory cytokine production, cell activation and recruitment, and osteoclastogenesis. Studies highlight the potential
importance of T helper 17 cells and regulatory T cells in driving and suppressing inflammation in rheumatoid arthritis, respectively,
and highlight other potential T-cell therapeutic targets. The genetic associations of the HLA shared epitope alleles with
antibodies to citrullinated peptides in rheumatoid arthritis patients indicate that T cells are providing help to B cells
to produce autoantibodies, and there is increasing evidence that these autoantibodies are pathogenic in rheumatoid arthritis. 相似文献
14.
Douglas James Veale 《Arthritis research & therapy》2013,15(6):224
Psoriatic arthritis (PsA) is the second most common inflammatory arthropathy, after
rheumatoid arthritis diagnosis, in early arthritis clinics. Most patients have
established psoriasis, often for years, prior to the onset of joint pain and
swelling; in addition, associated features of nail disease, dactylitis, enthesitis,
spondylitis or uveitis may be present. Psoriasis may not be immediately apparent, as
small or patchy lesions may occur in the scalp or perineum. PsA presents as a
symmetrical polyarthritis, similar to rheumatoid arthritis, or an asymmetrical
oligoarthritis with a predilection for the distal interphalangeal joints. Spinal
involvement is similar, although not identical, to ankylosing spondylitis. Joint
damage occurs early; up to 50% of PsA patients have an 11% annual erosion rate in the
first 2 years of disease duration, suggesting it is not a benign condition.
There have been significant advances in our understanding of PsA pathogenesis in
recent years, in the areas of genetics and molecular biology, implicating both the
innate and the adaptive immune systems. This has lead to the introduction of
evidence-based targeted therapy, primarily with tumour necrosis factor inhibitor
(TNFi) agents. Therapy with disease-modifying anti-rheumatic drugs, such as
methotrexate and leflunomide, remains the first-choice therapeutic intervention, even
though there are few randomised controlled trials with these agents. In contrast, a
number of successful studies of TNFi agents demonstrate excellent efficacy, in
combination with methotrexate, and several novel agents are currently in development
for the treatment of PsA. 相似文献
15.
This study is to determine the role and mechanism of crocin in rheumatoid arthritis (RA). Totally 60 Wistar SD rats were randomly divided into control group, RA model group, methotrexate group, crocin high dose, middle dose, and low dose groups. The paw swelling degree, arthritis score, thymus and spleen index, the mRNA and protein levels of iNOS, and the serum content of TNF-α, IL-1β, and IL-6 were evaluated. Crocin treatment significantly alleviated the paw swelling of RA rats. The arthritis score in crocin treatment groups was significantly lower than that in RA model group. Additionally, the thymus index, but not the spleen index, declined remarkably in crocin treatment groups than in RA model group. Besides, crocin administration significantly reduced the iNOS production and the serum content of TNF-α, IL-1β, and IL-6. Crocin may exert potent anti-RA effects through inhibiting cytokine. 相似文献
16.
Maity S Ullanat R Lahiri S Shekar S Sodhan G Vyas A Dyaga G Ireni S Nair N Sotsios Y Maria DC Morawala-Patell V 《Biologicals》2011,39(6):384-395
Etanercept is a soluble tumor necrosis factor (TNF) receptor originally approved for treatment of moderate-to-severe rheumatoid arthritis, juvenile rheumatoid arthritis, and psoriatic arthritis. We have developed a non-innovator version of the recombinant protein etanercept, with the investigational name AVG01 (trade name AVENT™), using a novel expression vector-based technology. Here we show, by extensive analytical characterization, that AVG01 is highly similar to the reference product Enbrel® and demonstrates similar efficacy in pre-clinical studies. 相似文献
17.
Forrest CM Stone TW Mackay GM Oxford L Stoy N Harman G Darlington LG 《Nucleosides, nucleotides & nucleic acids》2006,25(9-11):1287-1290
The anti-inflammatory activities of methotrexate and sulphasalazine may be mediated by increases in endogenous adenosine levels. Since the vascular protective drug dipyridamole inhibits the uptake and metabolism of adenosine we have now tested this compound in patients with rheumatoid arthritis to assess its effects on their symptoms. Forty patients (aged 18-75 years) received dipyridamole 400 mg/day or placebo. The levels of adenosine and its major metabolites were determined by high performance liquid chromatography (HPLC) in blood samples taken at baseline and at monthly intervals during treatment for 6 months. After three months of treatment there was a significant reduction in the modified Health Assessment Questionnaire (mHAQ) score, but these effects were not maintained, and dipyridamole did not modify disease severity scores or the levels of adenosine and its metabolites. We conclude that the symptoms of rheumatoid arthritis were not modified by treatment with dipyridamole. 相似文献
18.
Rheumatoid arthritis (RA) is an autoimmune disease characterized by a chronic inflammation of the synovial joints and infiltration of blood-derived cells. In daily practice rheumatologists use the antimetabolites methotrexate (MTX) and leflunomide for the treatment of patients with rheumatoid arthritis. The current clinical status (efficacy/toxicity) of these 2 antimetabolites in the treatment of RA will be discussed. 相似文献
19.
Besides atherosclerosis and lung cancer, smoking is considered to play a major role in the pathogenesis of autoimmune diseases.
It has long been known that there is a connection between rheumatoid factor-positive rheumatoid arthritis and cigarette smoking.
Recently, an important gene–environment interaction has been revealed; that is, carrying specific HLA-DRB1 alleles encoding
the shared epitope and smoking establish a significant risk for anti-citrullinated protein antibody-positive rheumatoid arthritis.
We summarize how smoking-related alteration of the cytokine balance, the increased risk of infections (the possibility of
cross-reactivity) and modifications of autoantigens by citrullination may contribute to the development of rheumatoid arthritis. 相似文献
20.