931 resultados para Il-2
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O objetivo deste estudo foi determinar os níveis de interleucina-1β (IL-1 β), IL-2, IL-4, IL-8, interferon-γ (IFN-γ) e a atividade de elastase no fluido gengival (FG) de pacientes com periodontite crônica generalizada (PCG) e periodontite agressiva generalizada (PAgG), e correlacionar com indivíduos de um grupo controle com gengivite apenas. Um objetivo secundário foi analisar o perfil microbiológico subgengival destes indivíduos. Dados clínicos transversais foram obtidos de 20 pacientes com PCG, 17 pacientes com PAgG e 10 indivíduos com gengivite. Amostras de FG foram coletadas com tiras de papel e os níveis de: IL-1β, IL-2, IL-4, IL-8 e IFN-γ foram medidos, utilizando um imunoensaio do tipo multiplex (Luminex). Atividade da elastase foi avaliada por um ensaio enzimático. Amostras de placa subgengival foram analisadas através do checkerboard DNA-DNA hybridization. As diferenças de significância entre os grupos para dados imunológicos e microbiológicos foram realizadas utilizando o teste Kruskal-Wallis, ajustando para múltiplas comparações. As médias dos parâmetros clínicos e os volumes de FG foram maiores nos pacientes com PCG e PAgG comparados ao grupo gengivite. Níveis mais elevados de IL-1β e atividade de elastase foram encontrados em sítios profundos quando comparado a sítios rasos em ambos os grupos com periodontite (p <0,05). Os dados microbiológicos apresentaram níveis significativamente mais elevados das espécies do complexo vermelho em pacientes com PCG e PAgG, quando comparados aos indivíduos com gengivite (p <0,05). Não houve diferença estatisticamente significante nos níveis de biomarcadores no FG e nos níveis de espécies bacterianas subgengivais entre pacientes com PCG e pacientes com PAgG. Sendo assim, concluímos que os dados do presente estudo não mostraram diferença estatisticamente significante nos parâmetros imunológicos e microbiológicos medidos entre indivíduos com PCG e PAgG.
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252 p. : il.
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Background: An accumulating body of evidence points to the significance of neuroinflammation and immunogenetics in schizophrenia, and an imbalance of cytokines in the central nervous system (CNS) has been suggested to be associated with the disorder. Munc18-overexpressing mice (Munc18-OE) have provided a model for the study of the alterations that may underlie the symptoms of subjects with schizophrenia. The aim of the present study was to elucidate the involvement of neuroinflammation and cytokine imbalance in this model. Methods: Cytokines were evaluated in the cortex and the striatum of Munc18-OE and wild-type (WT) mice by enzyme-linked immunosorbent assay (ELISA). Protein levels of specific microglia and macrophage, astrocytic and neuroinflammation markers were quantified by western blot in the cortex and the striatum of Munc18-OE and WT mice. Results: Each cytokine evaluated (Interferon-gamma (IFN-gamma), Tumor Necrosis Factor-alpha (TNF-alpha), Interleukin-2 (IL-2) and CCL2 chemokine) was present at higher levels in the striatum of Munc18-OE mice than WT. Cortical TNF-alpha and IL-2 levels were significantly lower in Munc18-OE mice than WT mice. The microglia and macrophage marker CD11b was lower in the cortexes of Munc18-OE mice than WT, but no differences were observed in the striatum. Glial Fibrillary Acidic Protein (GFAP) and Nuclear Factor-kappaB (NF-kappa B)p65 levels were not different between the groups. Interleukin-1beta (IL-1 beta) and IL-6 levels were beneath detection limits. Conclusions: The disrupted levels of cytokines detected in the brain of Munc18-OE mice was found to be similar to clinical reports and endorses study of this type for analysis of this aspect of the disorder. The lower CD11b expression in the cortex but not in the striatum of the Munc18-OE mice may reflect differences in physiological activity. The cytokine expression pattern observed in Munc18-OE mice is similar to a previously published model of schizophrenia caused by maternal immune activation. Together, these data suggest a possible role for an immune imbalance in this disorder.
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Após o estímulo deflagrador de um trauma ou infecção, a liberação de citocinas na circulação sanguínea desempenha um importante papel efetor e também modulador da resposta imune sistêmica. Essas citocinas podem ser pró-inflamatórias, que estimulam a liberação de diversos tipos celulares e de outras citocinas, como fator de necrose tumoral-alfa (TNF-α), interleucina 1 (IL-1), IL-2, IL-6, IL-8, IL-12 e interferon-gama (INF-); ou citocinas com efeitos antiinflamatórios, que inibem o processo inflamatório, em parte pela redução da produção de diversas citocinas que regulam positivamente a resposta, minimizando o comprometimento orgânico resultante, como IL-4, IL-10, IL-13. A L-glutamina é o aminoácido mais abundante no organismo, com importante papel no metabolismo protéico. Sua ação trófica sobre a mucosa do intestino delgado é bastante conhecida, o que o torna componente essencial para a manutenção estrutural e funcional do intestino. O objetivo deste trabalho foi avaliar o efeito da suplementação dietética com L-glutamina na modulação da resposta inflamatória em animais submetidos a sepse abdominal induzida por ligadura e perfuração cecal. Foram utilizados 24 ratos Wistar machos adultos, com peso inicial entre 200 e 230 g, distribuídos em três grupos, cada um com oito animais, da seguinte forma: grupo I (controle) submetidos a operação simulada (laparotomia e manipulação de alças intestinais); grupo II submetidos a laparotomia, com indução de sepse abdominal; e grupo III receberam suplementação dietética com L-glutamina por sete dias e, após, foram submetidos a indução de sepse abdominal. Foram coletadas amostras sanguíneas de todos os animais antes (tempo 0) e duas e quatro horas (tempos 1 e 2) após a indução da sepse abdominal. Foram verificados o número de leucócitos, a dosagem da concentração plasmática de citocinas pró- e antiinflamatórias (INF-γ, IL-6 e IL-10) e análise microbiológica de líquido peritoneal. A glicemia apresentou aumento significativo em todos os grupos, comparando-os ao início e ao final do experimento (p<0,05). No que concerne à IL-10, observou-se aumento significativo nos animais do grupo III entre os tempos 0 e 2, e entre os tempos 1 e 2 (p=0,0331 e p=0,0155, respectivamente). Não se observou qualquer outra diferença ao serem analisadas as demais citocinas (IFN- e IL-6), em todos os grupos e em todos os momentos analisados. Nossos achados sugerem que a suplementação dietética com L-glutamina em animais submetidos à indução de sepse abdominal com modelo CLP parece potencializar a resposta antiinflamatória, aumentando a concentração plasmática de IL-10, enquanto as concentrações de INF-γ e IL-6 não apresentaram variação significativa.
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选取天然产物虎眼万年青作为研究对象,对一其化学成分及药理活性进行了系统的研究。针对不同成分极性的显著差异,分离、纯化出13种化合物,并鉴定了其中的弱极性的小分子物质。采用COZ超临界提取技术,对易挥发的19种成分分别作了鉴定。对其中具有药理活性的多糖、皂营及生物碱等成分,经进一步分离、纯化,并借助现代波谱技术,对其单一成分进行了跟踪、表征。研究了虎眼万年青不同组分的抗肿瘤、抗辐射作用。首次筛选出了有显著药理活性的虎眼万年青中性多糖53,并从非特异性免疫功能、体液免疫功能和细胞免疫功能等角度,即从细胞和分子水平较全面地研究了S3的免疫增强作用。结果表明,53能显著增强小鼠T淋巴细胞的转化、提高NK细胞细胞毒活性,不同程度的使CD3、CD4、CD4/CDS升高而使CDS下降,从分子水平证实了S3对辅助性T细胞(Th)的增强作用及对抑制性T细胞(Ts)的降低作用,推测Tl:可能是其主要的原发刺激细胞。此外,S3不仅能促进细胞因子IL-2的产生,还能使IL-1mRNA基因表达量显著增加,从基因水平进一步证实了53有提高小鼠免疫功能的作用。首次利用电喷雾质谱(ESI-MS),在较温和的条件下得到了具有较高稳定性的新型簇合物离子K+K(NO3)n:和NO3-(KNO3)m。并利用现代量子化学程序对低聚合度簇合物离子的可能组态进行了总成键能的计算,给出了相对稳定的组态。计算结果说明,n=2,3,6组态稳定性高的原因是总成键能高,而m≤4阴离子簇合物不能直接形成的原因是由于溶剂化作用。电喷雾质谱的进样过程与晶体的成核过程相类似,通过气相离子簇合物的组态信息和形成机理的研究,可以为晶体成核理论和化学键理论提供某些证据。
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神经节甘脂GD2在正常的组织细胞中很少存在,而在黑色索瘤、小细胞肺癌、等肿瘤细胞表面大量存在。因此能特异性结合神经节营脂GD2,激活肿瘤附近免疫细胞功能的基因工程融合蛋白将为上述肿瘤的治疗开辟新的途径。实验中采用重叠PCR技术,将抗神经节普脂GDZ的单链抗体和抗CD16(FcyRIIIA)分子的单链抗体用(GGGG4s)3和sGGGGs两种连接肤连接,形成两个新型的anti-GD2/anti-CD16单链双特异性抗体基因N1M1和N2M2,将重组基因分别连接表达载体PSE380和pET22b(+),得到重组质粒PSE380-N1M1/pSE380-N2M2和pET22b(+)-N1M1/pET22b(+)-N2M2。psE380-N1M1/pSE380-N2M2转化BL21后诱导表达,表达后的单链双特异性抗体以包涵体的形式存在于细胞中。pET22b(+)-N1M1/pET22b(+)-N2M2转化大肠杆菌BL21(DE3),表达的单链双特异性抗体以可溶形式存在于细胞的周质空问。实验中选择BL21(DE3)/pET22b(+)-N1M1和BL21(DE3)/pET22b(+)-N2M2作为双」亢的生产菌株,经均匀设计优化诱导条件后,两个单链双特异性抗体nlml和n2m2的表达量均可达菌体总蛋白的30%左右,分子量分别为54KD和53KD。实验中选择经过突变改变过的人IL-2(125Ala)与抗GDZ单链抗体触合,构建了副:合蛋白基因IL-2-M,连接表达载体PSE38。,重组质粒转化BI,21菌株,得到工程菌BL21/pSE38O-IL-2-M,诱等农达后,触合蛋白IL-2-m以包涵体的形式存在于细胞中,表达量约占菌体总蛋白的30%,分子量为43KD。IISA分析表明,诱导后表达的融合蛋白可与hIL-2抗体特异性结合。采用Ni-NTA亲和层析和分子筛层析纯化上述三种融合蛋自,纯度可达95%以上。用LDH法检测其对肿瘤的杀伤作月」,实验结果证明:实验构建的中.链双特异性抗体nlml和112m2均可以激活单个核细胞(PBMC),杀伤GDZ阳性肿瘤细胞:IL-2与抗GDZ单链抗体融合蛋白IL-2-m对GD2阳性肿瘤细胞也起到一定的杀伤作用;anti-GD2/anti-CD16单链双特异性抗体与融合蛋白IL-2-m联用效果史为显著。
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The aim of this study was to estimate the acute effects of low dose C-12(6+) ions or X-ray radiation on human immune function. The human peripheral blood lymphocytes (HPBL) of seven healthy donors were exposed to 0.05 Gy C-12(6+) ions or X-ray radiation and cell responses were measured at 24 h after exposure. The cytotoxic activities of HPBL were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT); the percentages of T and NK cells subsets were detected by flow cytometry; mRNA expression of interleukin (IL)-2, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma were examined by real time quantitative RT-PCR (qRT-PCR); and these cytokines protein levels in supematant of cultured cells were assayed by enzyme-linked immunosorbent assays (ELISA). The results showed that the cytotoxic activity of HPBL, mRNA expression of IL-2, IFN-gamma and TNF-alpha in HPBL and their protein levels in supernatant were significantly increased at 24 h after exposure to 0.05 Gy C-12(6+) ions radiation and the effects were stronger than observed for X-ray exposure. However, there was no significant change in the percentage of T and NK cells subsets of HPBL. These results suggested that 0.05 Gy high linear energy transfer (LET) C-12(6+) radiation was a more effective approach to host immune enhancement than that of low LET X-ray. We conclude that cytokines production might be used as sensitive indicators of acute response to LDL (C) 2009 COSPAR. Published by Elsevier Ltd. All rights reserved.
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经Ficoll-Hypaque分离从癌性胸水中获得的淋巴细胞,在体外含IL-2的培养条件下激活成为PEAL;后者具有正常人二倍体细胞核型,胞质中可见电子致密、大小不等的膜包二硫键阳性颗粒,可能属于穿孔素。PEAL的增殖依赖于一定浓度IL-2的存在。其对K562和Raji的细胞毒活性高峰大多处于培养的10~20天。胸腔局部应用rIL-2预刺激后所诱导的PEAL细胞毒活性较高,增殖也较为旺盛,PEAL细胞经济易得,对肿瘤细胞有较强的杀伤活性,在体外能进一步扩增,是一种较为适合于继承性免疫治疗的抗瘤效应细胞。
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依据虎眼万年青组分中多糖对小鼠巨噬细胞吞噬功能的影响,筛选并优化出60%醇浓度中性多糖活性组分S3,进而研究其对体液免疫、细胞免疫及细胞因子变化的影响,并从细胞和分子水平探讨其作用的机理.方法:采用溶血素测定方法,测定S3对小鼠脾细胞溶血素抗体的诱导作用;采用3H-TdR渗入法,测定S3对ConA诱导小鼠脾淋巴细胞的增殖作用;采用3H-TdR后标记法,测定S3对NK细胞细胞毒活性的影响;以ELISA法测定S3对小鼠脾细胞IL-2产生的影响;利用流式细胞术,检测S3对T淋巴细胞亚群CD3、CD4、CD8、CD4/CD8阳性细胞百分率的影响;采用RT-PCR方法检测IL-2 mBNA的表达水平.结果:S3高、中剂量组能明显增强小鼠脾细胞溶血素抗体的形成(P<0.05);各剂量组均能明显增强ConA诱导的淋巴细胞增殖能力(P<0.001);各剂量组均能增强NK细胞的细胞毒活性并促进IL-2的产生(P<0.001,P<0.01);高、中剂量组CD8阳性细胞百分率明显降低(P<0.001),各剂量组均能显著地提高CD4/CD8阳性细胞百分率(P<0.001);高剂量组可明显促进脾细胞中细胞因子IL-2的mRNA表达,使表达量增加(P<0.05).结论:S3具有较强的增强机体多种免疫功能的作用,可利用开发为一种免疫增强药物.
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The modulation of carrageenan oligosaccharides from Kappaphycus striatum on the immune system in S 180-bearing mice was investigated. The mice inoculated with S180 cell suspension were treated p.o. with carrageenan oligosaccharides (50, 100 and 200 mu g/g) for 14 days. The effects of carrageenan oligosaccharides on transplantable tumors and macrophage phagocytosis, quantitative hemolysis of sheep red blood cells (QHS),. lymphocyte proliferation, the activity of natural killer cells (NK), production of interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-alpha) were studied. Carrageenan oligosaccharides could significantly inhibit the growth of transplantable sarcoma S180 and increase macrophage phagocytosis, the form of antibody secreted by spleen cells, spleen lymphocyte proliferation, NK cells activity, serumal IL-2 and TNF-alpha level in S 180-bearing mice. Considering all these results, it is suggested that carrageenan oligosaccharides exert their antitumor effect by promoting the immune system. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
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目的 了解塞隆骨水提物(SLG—B)对胶原诱导的小鼠关节炎的治疗作用及治疗机制。方法 利用牛Ⅱ型胶原诱导DBA/1小鼠类风湿性关节炎模型即CIA。SLG—B口服给药观察小鼠关节炎指数的变化情况,体外培养关节炎小鼠脾细胞及巨噬细胞,ELISA法测定IL-12、IL-2、IFN-γ TNF-α几种细胞因子。RT-PCR测定SLG-B对关节炎小鼠巨噬细胞IL-1β、IL-6、iNOS mRNA表达的影响。结果 SLG-B能明显的抑制牛Ⅱ型胶原诱导关节炎的发生,能够减轻关节炎的各种症状。SLG-B在加抗原和不加抗原的情况下都能够明显的抑制关节炎小鼠脾细胞的增殖同时发现SLG-B能够抑制IL-2、IFN-1、L-12p40、TNF-α细胞因子的产生。还能够抑制小鼠腹腔巨噬细胞IL-1、IL-6及iNOS mRNA的表达。这可能是SLG—B在小鼠关节炎中表现治疗效果的分子基础。结论 SLG—B对小鼠关节炎有很好的治疗效果,其作用机制主要是通过抑制巨噬细胞及脾细胞产生炎性细胞因子和抑制炎性细胞因子mRNA的表达来达到治疗类风湿性关节炎的作用。
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O greening, inicialmente chamado de "doenças do ramo amarelo", e posteriomente huanglonbing (HBL), doença do dragão amarelo, é considerada a doença dos citros de maior importância no mundo, em função da dificuldade de controle, da rápida disseminação e por ser altamente destrutiva. O primeiro relato da doença foi feito da China, em 1919, espalhando-se daí para países da África e Oceania. No início do século 21, foi detectada no continente americano, exatamente nos dois países e estados maiores produtores de citros: os Estados Unidos (Flórida) e o Brasil (São Paulo) onde foi relatada em Araraquara em 2004, estando hoje em mais de 100 municípios produtores.
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Algumas espécies de ácaros encontram-se associadas com a cultura da mandioca (Manihot esculenta Crantz), com destaque para fitófagos pertencentes à família Tetranychidae. No Brasil, as seguintes espécies de Tetranychidae foram relatadas na cultura: Aponychus Shultzi, Mononychellus bondari, M. mcgregori, M. planki, M. tanajoa, Tetranychus desertorum, T. mexicanus e T. urticae. Dentre estas, merecem destaque o ácaro verde da mandioca, M. tanajoa, e o ácaro-rajado, T. urticae. Tetranychus urticae é da ampla distribuição geográfica e de ocorrência em várias culturas além de mandioca. Em geral as fêmeas apresentam cor esverdeada é encontrado na face inferior das folhas, preferencialmente nas partes medianas e basal da planta. As folhas atacadas apresentam na face superior pontos amarelados ao longo da nervura central se estendendo por toda folha, adquirindo coloração bronzeada; posteriormente secam e caem. Em ataques severos pode ocorrer perda das folhas basais e medianas da planta, avançando até a parte apical.
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Functional food ingredients, with scientifically proven and validated bioactive effects, present an effective means of inferring physiological health benefits to consumers to reduce the risk of certain diseases. The search for novel bioactive compounds for incorporation into functional foods is particularly active, with brewers’ spent grain (BSG, a brewing industry co-product) representing a unique source of potentially bioactive compounds. The DNA protective, antioxidant and immunomodulatory effects of phenolic extracts from both pale (P1 - P4) and black (B1 – B4) BSG were examined. Black BSG extracts significantly (P < 0.05) protected against DNA damage induced by hydrogen peroxide (H2O2) and extracts with the highest total phenolic content (TPC) protected against 3-morpholinosydnonimine hydrochloride (SIN-1)-induced oxidative DNA damage, measured by the comet assay. Cellular antioxidant activity assays were used to measured antioxidant potential in the U937 cell line. Extracts P1 – P3 and B2 - B4 demonstrated significant (P < 0.05) antioxidant activity, measured by the superoxide dismutase (SOD) activity, catalase (CAT) activity and gluatathione (GSH) content assays. Phenolic extracts P2 and P3 from pale BSG possess anti-inflammatory activity measured in concanavalin-A (conA) stimulated Jurkat T cells by an enzyme-linked immunosorbent assay (ELISA); significantly (P < 0.05) reducing production of interleukin-2 (IL-2), interleukin-4 (IL-4, P2 only), interleukin-10 (IL-10) and interferon-γ (IFN-γ). Black BSG phenolic extracts did not exhibit anti-inflammatory effects in vitro. Hydroxycinnamic acids (HA) have previously been shown to be the phenolic acids present at highest concentration in BSG; therefore the HA profile of the phenolic extracts used in this research, the original barley (before brewing) and whole BSG was characterised and quantified using high performance liquid chromatography (HPLC). The concentration of HA present in the samples was in the order of ferulic acid (FA) > p-coumaric acid (p-CA) derivatives > FA derivatives > p-CA > caffeic acid (CA) > CA derivatives. Results suggested that brewing and roasting decreased the HA content. Protein hydrolysates from BSG were also screened for their antioxidant and anti-inflammatory potential. A total of 34 BSG protein samples were tested. Initial analyses of samples A – J found the protein samples did not exert DNA protective effects (except hydrolysate H) or antioxidant effects by the comet and SOD assays, respectively. Samples D, E, F and J selectively reduced IFN-γ production (P < 0.05) in Jurkat T cells, measured using enzyme linked immunosorbent assay (ELISA). Further testing of hydrolysates K – W, including fractionated hydrolysates with molecular weight < 3, < 5 and > 5 kDa, found that higher molecular weight (> 5 kDa) and unfractionated hydrolysates demonstrate greatest anti-inflammatory effects, while fractionated hydrolysates were also shown to have antioxidant activity, by the SOD activity assay. A commercially available yogurt drink (Actimel) and snack-bar and chocolate-drink formulations were fortified with the most bioactive phenolic and protein samples – P2, B2, W, W < 3 kDa, W < 5 kDa, W > 5 kDa. All fortified foods were subjected to a simulated gastrointestinal in vitro digestion procedure and bioactivity retention in the digestates was determined using the comet and ELISA assays. Yogurt fortified with B2 digestate significantly (P < 0.05) protected against H2O2-induced DNA damage in Caco-2 cells. Greatest immunomodulatory activity was demonstrated by the snack-bar formulation, significantly (P < 0.05) reducing IFN-γ production in con-A stimulated Jurkat T cells. Hydrolysate W significantly (P < 0.05) increased the IFN-γ reducing capacity of the snack-bar. Addition of fractionated hydrolysate W < 3 kDa and W < 5 kDa to yogurt also reduced IL-2 production to a greater extent than the unfortified yogurt (P < 0.05).
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Introduction: There is accumulating evidence of an increased risk of cardiovascular morbidity and mortality in rheumatoid arthritis patients. A combination of both traditional cardiovascular risks and rheumatoid specific factors appear to be responsible for driving this phenomenon. Rheumatoid arthritis has been an orphan of cardiologists in the past and rheumatologists themselves are not good at CVD screening. Identifying the extent of preclinical atherosclerosis in RA patients will help us to appreciate the magnitude of this serious problem in an Irish population. Methods: We undertook a cross-sectional study of 63 RA patients and 48 OA controls and compared the 2 groups with respect to 1) traditional CV risks factors, 2) serum biomarkers of inflammation, including CRP, TNFα, IL6 and PAI-1, 3) carotid intima-media thickness (cIMT), carotid plaque and ankle-brachial index (ABI) as markers of pre-clinical atherosclerosis, 4) biochemical and ultrasonic measures of endothelial dysfunction and 5) serum and echocardiographic measures of diastolic dysfunction. Within the RA group, we also investigated for associations between markers of inflammation, subclinical atherosclerosis and diastolic dysfunction. Results: Prevalence of traditional CV risks was similar in the RA and OA groups. A number of biomarkers of inflammation were significantly higher in the RA group: CRP, fibrinogen, IL- 2, -4, -6, TNFα. PAI-1, a marker of thrombosis, correlated with disease activity and subclinical atherosclerosis in RA patients. With regard to subclinical atherosclerosis measures, RA patients had a significantly lower ABI than OA patients. Carotid plaque and cIMT readings were similar in RA and OA patients. Assessment of endothelial function revealed that RA patients had significantly higher concentrations of adhesion molecules, in particular sero-positive RA patients and RA smokers. Adhesion molecule concentrations were associated with markers of diastolic dysfunction in RA. Urine PCR, another marker of endothelial dysfunction also correlated with diastolic dysfunction in RA. Assessment of endothelial function with flow mediated dilatation (FMD) found no difference between the RA and OA groups. Disease activity scores in RA patients were associated with endothelial dysfunction, as assessed by FMD. Conclusions: We did not find significant differences in measures of subclinical atherosclerosis, flow mediated dilatation or diastolic function between RA and OA patients. This is most likely in part due to the fact that there is increasing evidence that OA has an inflammatory component to its pathogenesis and is associated with metabolic syndrome and increased CV risk. We reported a significant association between urinary PCR and measures of diastolic dysfunction. Urinary PCR may be a useful screening tool for diastolic dysfunction in RA. The association between RA disease activity and measures of vascular function supports the theory that the excess cardiovascular burden in RA is linked to uncontrolled inflammation.