S Gertel, M Rokach, A Polachek, I Litinsky, M Anouk, O Elkayam, V Furer
{"title":"英夫利昔单抗和甲氨蝶呤对外周血和滑膜液单核细胞的抗炎作用:体外研究。","authors":"S Gertel, M Rokach, A Polachek, I Litinsky, M Anouk, O Elkayam, V Furer","doi":"10.1080/03009742.2023.2300887","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>To investigate the effects of methotrexate (MTX) and the tumour necrosis factor inhibitor infliximab (IFX) on immune cells derived from peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) of inflammatory arthritis patients.</p><p><strong>Method: </strong>Phytohaemagglutinin (PHA)-induced proliferation of healthy donors' PBMCs and synovial intermediate monocytes (CD14<sup>+</sup>CD16<sup>+</sup> cells) in SFMCs derived from psoriatic arthritis (PsA) and rheumatoid arthritis (RA) patients was determined by flow cytometry following co-culture with IFX and MTX. PHA-induced interferon-γ (IFN-γ) production in PBMCs was measured by enzyme-linked immunosorbent assay. The drugs' effect on mRNA expression in SFMCs was determined by quantitative polymerase chain reaction.</p><p><strong>Results: </strong>The combination of IFX 10 μg/mL + MTX 0.1 μg/mL had the strongest inhibitory effect on PBMC proliferation (91%), followed by MTX 0.1 μg/mL (86%) and IFX 10 μg/mL (49%). In PHA-stimulated PBMCs, IFN-γ production was reduced by IFX 10 μg/mL, MTX 0.1 μg/mL, and IFX 10 μg/mL + MTX 0.1 μg/mL by 68%, 90%, and 85%, respectively. In SFMCs, IFX 10 µg/mL significantly reduced CD14<sup>+</sup>CD16<sup>+</sup> cells compared to medium (PsA 54%, p < 0.01; RA 46%, p < 0.05), while MTX had no effect on this population. IFX + MTX led to a similar suppression of CD14<sup>+</sup>CD16<sup>+</sup> cells as achieved by IFX alone. The drugs had different impacts on SFMC gene expression.</p><p><strong>Conclusion: </strong>Both IFX and MTX effectively inhibited PBMC proliferation and IFN-γ production, but only IFX reduced synovial monocytes and pro-inflammatory gene expression in SFMCs, suggesting a differential impact of IFX and MTX on critical inflammatory cell populations ex vivo.</p>","PeriodicalId":21424,"journal":{"name":"Scandinavian Journal of Rheumatology","volume":" ","pages":"188-198"},"PeriodicalIF":2.2000,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Anti-inflammatory effects of infliximab and methotrexate on peripheral blood and synovial fluid mononuclear cells: ex vivo study.\",\"authors\":\"S Gertel, M Rokach, A Polachek, I Litinsky, M Anouk, O Elkayam, V Furer\",\"doi\":\"10.1080/03009742.2023.2300887\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>To investigate the effects of methotrexate (MTX) and the tumour necrosis factor inhibitor infliximab (IFX) on immune cells derived from peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) of inflammatory arthritis patients.</p><p><strong>Method: </strong>Phytohaemagglutinin (PHA)-induced proliferation of healthy donors' PBMCs and synovial intermediate monocytes (CD14<sup>+</sup>CD16<sup>+</sup> cells) in SFMCs derived from psoriatic arthritis (PsA) and rheumatoid arthritis (RA) patients was determined by flow cytometry following co-culture with IFX and MTX. PHA-induced interferon-γ (IFN-γ) production in PBMCs was measured by enzyme-linked immunosorbent assay. The drugs' effect on mRNA expression in SFMCs was determined by quantitative polymerase chain reaction.</p><p><strong>Results: </strong>The combination of IFX 10 μg/mL + MTX 0.1 μg/mL had the strongest inhibitory effect on PBMC proliferation (91%), followed by MTX 0.1 μg/mL (86%) and IFX 10 μg/mL (49%). In PHA-stimulated PBMCs, IFN-γ production was reduced by IFX 10 μg/mL, MTX 0.1 μg/mL, and IFX 10 μg/mL + MTX 0.1 μg/mL by 68%, 90%, and 85%, respectively. In SFMCs, IFX 10 µg/mL significantly reduced CD14<sup>+</sup>CD16<sup>+</sup> cells compared to medium (PsA 54%, p < 0.01; RA 46%, p < 0.05), while MTX had no effect on this population. IFX + MTX led to a similar suppression of CD14<sup>+</sup>CD16<sup>+</sup> cells as achieved by IFX alone. The drugs had different impacts on SFMC gene expression.</p><p><strong>Conclusion: </strong>Both IFX and MTX effectively inhibited PBMC proliferation and IFN-γ production, but only IFX reduced synovial monocytes and pro-inflammatory gene expression in SFMCs, suggesting a differential impact of IFX and MTX on critical inflammatory cell populations ex vivo.</p>\",\"PeriodicalId\":21424,\"journal\":{\"name\":\"Scandinavian Journal of Rheumatology\",\"volume\":\" \",\"pages\":\"188-198\"},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2024-05-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Scandinavian Journal of Rheumatology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/03009742.2023.2300887\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/26 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"RHEUMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Scandinavian Journal of Rheumatology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/03009742.2023.2300887","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/26 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}
Anti-inflammatory effects of infliximab and methotrexate on peripheral blood and synovial fluid mononuclear cells: ex vivo study.
Objective: To investigate the effects of methotrexate (MTX) and the tumour necrosis factor inhibitor infliximab (IFX) on immune cells derived from peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) of inflammatory arthritis patients.
Method: Phytohaemagglutinin (PHA)-induced proliferation of healthy donors' PBMCs and synovial intermediate monocytes (CD14+CD16+ cells) in SFMCs derived from psoriatic arthritis (PsA) and rheumatoid arthritis (RA) patients was determined by flow cytometry following co-culture with IFX and MTX. PHA-induced interferon-γ (IFN-γ) production in PBMCs was measured by enzyme-linked immunosorbent assay. The drugs' effect on mRNA expression in SFMCs was determined by quantitative polymerase chain reaction.
Results: The combination of IFX 10 μg/mL + MTX 0.1 μg/mL had the strongest inhibitory effect on PBMC proliferation (91%), followed by MTX 0.1 μg/mL (86%) and IFX 10 μg/mL (49%). In PHA-stimulated PBMCs, IFN-γ production was reduced by IFX 10 μg/mL, MTX 0.1 μg/mL, and IFX 10 μg/mL + MTX 0.1 μg/mL by 68%, 90%, and 85%, respectively. In SFMCs, IFX 10 µg/mL significantly reduced CD14+CD16+ cells compared to medium (PsA 54%, p < 0.01; RA 46%, p < 0.05), while MTX had no effect on this population. IFX + MTX led to a similar suppression of CD14+CD16+ cells as achieved by IFX alone. The drugs had different impacts on SFMC gene expression.
Conclusion: Both IFX and MTX effectively inhibited PBMC proliferation and IFN-γ production, but only IFX reduced synovial monocytes and pro-inflammatory gene expression in SFMCs, suggesting a differential impact of IFX and MTX on critical inflammatory cell populations ex vivo.
期刊介绍:
Scandinavian Journal of Rheumatology is the official journal of the Scandinavian Society for Rheumatology, a non-profit organization following the statutes of the Scandinavian Society for Rheumatology/Scandinavian Research Foundation. The main objective of the Foundation is to support research and promote information and knowledge about rheumatology and related fields. The annual surplus by running the Journal is awarded to young, talented, researchers within the field of rheumatology.pasting
The Scandinavian Journal of Rheumatology is an international scientific journal covering clinical and experimental aspects of rheumatic diseases. The journal provides essential reading for rheumatologists as well as general practitioners, orthopaedic surgeons, radiologists, pharmacologists, pathologists and other health professionals with an interest in patients with rheumatic diseases.
The journal publishes original articles as well as reviews, editorials, letters and supplements within the various fields of clinical and experimental rheumatology, including;
Epidemiology
Aetiology and pathogenesis
Treatment and prophylaxis
Laboratory aspects including genetics, biochemistry, immunology, immunopathology, microbiology, histopathology, pathophysiology and pharmacology
Radiological aspects including X-ray, ultrasonography, CT, MRI and other forms of imaging.