METHOTREXATE ACTION IN RHEUMATOID ARTHRITIS: STIMULATION OF CYTOKINE INHIBITOR AND INHIBITION OF CHEMOKINE PRODUCTION BY PERIPHERAL BLOOD MONONUCLEAR CELLS
| Autor: | M. Baggiolini, H Towbin, N. J. Gerber, B. Dewald, C. Rordorf, Michael Seitz, Harald Gallati, Pius Loetscher |
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| Jazyk: | angličtina |
| Rok vydání: | 1995 |
| Předmět: |
Adult
Male Chemokine medicine.drug_class medicine.medical_treatment 610 Medicine & health Peripheral blood mononuclear cell Monocytes Arthritis Rheumatoid Rheumatology medicine Humans Pharmacology (medical) Interleukin 8 Aged biology business.industry Monocyte Middle Aged Receptor antagonist medicine.disease medicine.anatomical_structure Interleukin 1 receptor antagonist Cytokine Methotrexate Rheumatoid arthritis Immunology biology.protein Cytokines Female business |
| Zdroj: | Seitz, M.; Loetscher, P.; Dewald, B.; Towbin, H.; Rordorf, C.; Gallati, H.; Baggiolini, M.; Gerber, N. J. (1995). METHOTREXATE ACTION IN RHEUMATOID ARTHRITIS: STIMULATION OF CYTOKINE INHIBITOR AND INHIBITION OF CHEMOKINE PRODUCTION BY PERIPHERAL BLOOD MONONUCLEAR CELLS. Rheumatology, 34(7), pp. 602-609. Oxford University Press 10.1093/rheumatology/34.7.602 |
| DOI: | 10.1093/rheumatology/34.7.602 |
| Popis: | This open label study examines whether methotrexate (MTX) treatment modulates ex vivo synthesis of interleukin-1 receptor antagonist (IL-1ra), soluble tumour necrosis factor receptors (sTNFR p55 and p75), interleukin-1 beta (IL-1 beta), tumour necrosis factor alpha (TNF-alpha), interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) by peripheral blood mononuclear cells (PBMC) and whether changes reflect clinical response. Significant stimulation of IL-1ra and sTNFR p75 as well as inhibition of IL-8 production of PBMC were associated with clinical improvement observed in patients treated with MTX. When defining the characteristics of patients at study entry retrospectively in responders and non-responders, a significantly lower ratio of IL-1ra:IL-1 beta production before and its increase upon treatment was associated with clinical response in 13 patients compared to five patients not responding to MTX. In addition, clinical improvement was associated with decreased synthesis of IL-1 beta, TNF-alpha and IL-8 induced by bacterial lipopolysaccharide, IL-1 alpha and IL-1 beta in PBMC in vitro. These findings suggest that MTX therapy reverses the inflammatory type of rheumatoid arthritis (RA) blood mononuclear cells by stimulating cytokine inhibitor production while inhibiting inflammatory cytokine release at the same time. This may explain the powerful anti-inflammatory properties of low-dose MTX as observed in most RA patients. Pretreatment determination of the IL-1ra:IL-1 beta ratio in PBMC may be predictive with regard to a favourable therapeutic response and therefore may be useful for the selection of RA patients to be treated with MTX. |
| Databáze: | OpenAIRE |
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