Possibilities for preventive treatment in rheumatoid arthritis? Lessons from experimental animal models of arthritis: a systematic literature review and meta-analysis

Dekkers, Jacqueline; Schoones, Jan W.; Huizinga, T.W.J.; Toes, René E. M.; Mil, Annette H M van der Helm-van

doi:10.1136/annrheumdis-2016-209830

Cited by 41 publications

(36 citation statements)

References 51 publications

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“…Rheumatoid arthritis (RA) patients present with symmetrical, painful and disabling joint inflammation years after the immune system has made fundamental mistakes [1,2]. Over time, the inflammatory lesion, the rheumatoid pannus, causes irreversible damage to tendons, cartilage, and bone.…”

Section: Introductionmentioning

confidence: 99%

Metabolic signatures of T-cells and macrophages in rheumatoid arthritis

Weyand

Zeisbrich

Goronzy

2017

Current Opinion in Immunology

116

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In most autoimmune diseases, a decade-long defect in self-tolerance eventually leads to clinically relevant, tissue-destructive inflammatory disease. The pathogenic potential of chronic persistent immune responses during the pre-clinical and clinical phase is ultimately linked to the bioenergetic fitness of innate and adaptive immune cells. Chronic immune cell stimulation, high cellular turn-over, structural damage to the host tissue and maladaptive wound healing, all require a reliable supply of nutrients, oxygen, and biosynthetic precursors. Here, we use the model system of rheumatoid arthritis (RA) to discuss immunometabolism from the vantage point of T-cells and macrophages that encounter fundamentally different metabolic stress scenarios in the RA host. We outline the general principle that both insufficient nutrient supply, as well as nutrient excess generate cellular stress responses and guide immune function. ATPlow, NADPHhigh, ROSlow T-cells hyperproliferate and are forced into premature senescence. ATPhigh, ROShigh macrophages dimerize the glycolytic enzyme pyruvate kinase to amplify STAT3-dependent inflammatory effector functions. A corollary of this model is that simple nutraceutical interventions will be insufficient to re-educate the immune system in RA. Instead, interference with cell-type-exclusive and differentiation-stage-dependent metabolic setpoints will be needed to reprogram arthritogenic pathways.

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Section: Introductionmentioning

confidence: 99%

Metabolic signatures of T-cells and macrophages in rheumatoid arthritis

Weyand

Zeisbrich

Goronzy

2017

Current Opinion in Immunology

116

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“…We observed this in addition to a decreased concentration of IL-2 in cell supernatants (Supplementary Figure 1B), both canonical indicators of Th1 activation and autocrine signaling. The blockade to CD4 + T cell co-stimulation has proven to be an effective RA treatment and is the mechanism of action of abatacept, a biological immunotherapy used to treat clinically apparent RA [1,21]. CD28-CD80/86 interaction is an important therapeutic target as CD28 ligation leads not only to increased T cell proliferation and activation, but also to increased CD154 expression [28]; CD154 is a crucial ligand involved in the activation of B cells and other APCs.…”

Section: Discussionmentioning

confidence: 99%

“…Due to the large economic and physiological burden this disease places on its patients, research has become increasingly focused on ways to: 1) better identify those at risk prior to the onset of symptoms and use that information to more accurately predict RA development, and 2) identify and develop effective preventative treatments targeting RA during the pre-clinical phase of the disease and thereby delay the onset of clinical RA [6,[18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Berberine delays onset of collagen induced arthritis through T cell suppression

Vita¹,

Lyons²,

Aljobaily³

et al. 2019

Preprint

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RUNNING TITLE (less than 50 characters): Berberine delays onset of collagen arthritis model KEY WORDS (5 words not in the title): CIA, berberine, RA, autoimmune, T cell ABSTRACT (250 words or less): Previous evidence suggests that berberine (BBR), a clinically relevant plant-derived alkaloid, alleviates symptoms of clinically apparent collagen induced arthritis (CIA), and may have a prophylactic role from in vitro studies. Thus, we used a CIA model to determine if BBR merits further exploration as a prophylactic treatment for rheumatoid arthritis. Mice were treated with either 1 mg/kg/day of BBR or a vehicle (PBS) control via IP injections from day 0 to day 28, were left untreated (CIA control), or were in a non-arthritic control group. Incidence of arthritis in BBR mice was 40%, compared to 90% in the CIA and 80% in the PBS controls. Populations of B cells and T cells from the spleens and draining lymph nodes were examined from mice across treatment groups on day 14 and from the remaining mice on day 28 when arthritic signs and symptoms were expected to be apparent. BBR-treated mice had significantly reduced populations of CD4 + T cells, CXCR5 + T fh cells, and an increased proportion of T reg at both day 14 and day 28 endpoints, as well as decreased CD28 + and CD154 + CD4 + T cells at day 14. BBR-treated mice also experienced a significant reduction of CD19 + B cells in LNs at day 28. Additionally, BBR treatment resulted in significantly lower anti-collagen type II-specific (anti-CII) IgG2a and anti-CII total IgG serum concentrations. These results indicate a potential role for BBR as a prophylactic supplement, and that its effect may be mediated through T cell suppression, which indirectly affects B cell activity. and PBS controls ( Fig. 2B). When comparing anti-CII IgG levels between arthritic and nonarthritic mice within the BBR group specifically, however, anti-CI IgG1, IgG2a and total IgG were all significantly reduced in the non-arthritic mice compared to those who developed arthritis (Fig. 2C). Additionally, there appeared to be a vehicle-specific effect on circulating anti-CII IgG in which the administration of PBS with 0.01% DMSO elicited elevated levels of anti-CII IgG1 and total IgG in vehicle control mice ( Fig. 2A-B).Key CD4 + T cell population characteristics in response to berberine treatment-On day 14, we observed a significant reduction in populations of both CD4 + T cells and CXCR5 + T fh cells in the LNs and spleen of BBR-treated mice (Fig. 3A-B), as well as a reduction in the percentage of CD28 + and CD154 + CD4 + T cells in the spleen and LNs of BBR-treated mice (Fig. 3A-B). By the day 28 experimental endpoint we continued to observe a significant reduction in CD4 + T cells and CXCR5 + T fh cells in the spleen and LNs of BBR-treated mice ( Fig. 3C-D), however, there was no significant difference in the percentage of CD28 + and CD154 + CD4 + T cells between treatment groups (Fig 3C-D). Berberine treatment leads to increased proportion of FOXP3 + CD25 + CD4 + T cells-To examineBBRs effect on ...

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“…Можно полагать, что трансформация НДА в РА на фоне лечения МТ может быть связана не столько с недос-таточной эффективностью этого препарата, сколько с ис-пользованием короткого курса (1 год), применением не-достаточно эффективной дозы и таблетированной формы препарата, которая существенно уступает по эффективно-сти подкожной форме МТ [216]. Следует подчеркнуть, что эффективность МТ при РА, в том числе на ранней стадии заболевания, теоретически очень хорошо обоснована [216] и подтверждена многочисленными данными иссле-дований на модели экспериментального артрита [217]. Совсем недавно были представлены предваритель-ные результаты многоцентрового рандомизированного плацебоконтролируемого исследования PRAIRI (Prevention of clinically manifest Rheumatoid ArthrItis by B Cell Directed Therapy in the Earliest Phase of the Disease), в которое было включено 82 пациента с артралгиями и по-ложительными результатами АЦБ и РФ, у которых не бы-ло клинических проявлений артрита [212].…”

Section: таблицаunclassified

Problems of Rheumatoid Arthritis Immunopathology: Evolution of the Disease

Насонов¹

2017

rsp

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Possibilities for preventive treatment in rheumatoid arthritis? Lessons from experimental animal models of arthritis: a systematic literature review and meta-analysis

Abstract: Data of experimental studies in animal models of arthritis suggest that prophylactic and prearthritis treatment strategies are effective and hint at differences in efficacy between antirheumatic drugs.

Cited by 41 publications

References 51 publications

Metabolic signatures of T-cells and macrophages in rheumatoid arthritis

Metabolic signatures of T-cells and macrophages in rheumatoid arthritis

Berberine delays onset of collagen induced arthritis through T cell suppression

Problems of Rheumatoid Arthritis Immunopathology: Evolution of the Disease

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