Titre du document / Document title

Interleukin-10 functions as an antiinflammatory cytokine in rheumatoid synovium

Auteur(s) / Author(s)

ISOMÄKI P. ⁽¹⁾ ; LUUKKAINEN R. ; SAARIO R. ; TOIVANEN P. ⁽¹⁾ ; PUNNONEN J. ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Turku University, Turku, FINLANDE

Résumé / Abstract

Objective. Interleukin-10 (IL-10) is an antiinflammatory cytokine that has been shown to play a role in rheumatoid arthritis (RA). We therefore investigated the effects of IL-10 on the function and phenotype of synovial fluid mononuclear cells (SFMC) derived from patients with RA. In addition, we studied the production of IL-10 in rheumatoid joints, and the role of endogenous IL-10 in the regulation of SFMC function. Methods. The presence of IL-10 in rheumatoid joints was studied using IL-10-specific enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase-polymerase chain reaction (RT-PCR) techniques. The effects of recombinant human IL-10 or neutralizing anti-IL-10 monoclonal antibodies (MAbs) on both cytokine production and phenotype of SFMC were evaluated using cytokine-specific ELISAs and flow cytometry. The effect of IL-10 on proliferation of SFMC was determined by incorporation of tritiated thymidine. Results. IL-10 was detected by ELISA in 22 of 23 SF samples, and was spontaneously produced by cultured SFMC. IL-10 messenger RNA was detectable in all 8 SFMC samples, as determined by RT-PCR. Neutralization of endogenously produced IL-10 by anti-IL-10 MAbs resulted in increased production of IL-1β, tumor necrosis factor α (TNFα), and granulocyte-macrophage colony-stimulating factor (GM-CSF) by SFMC, and in enhanced proliferation of SFMC. In particular, the production of TNFα was dramatically increased by anti-IL-10 MAbs. Moreover, the expression of HLA-DR molecules by SF macrophages was increased, and the expression of CD16 was decreased by anti-IL-10 MAbs. In contrast, addition of recombinant IL-10 significantly decreased the production of IL-1β, TNFα, and GM-CSF by SFMC, and decreased spontaneous and IL-2-induced proliferation of SFMC. Finally, IL-10 decreased HLA-DR expression and increased the expression of the Fcγ receptors, CD16 and CD64, by SF macrophages. Conclusion. These data indicate that endogenously produced IL-10 functions as an immunoregulatory molecule in rheumatoid synovium. Importantly, exogenous IL-10 has potent antiinflammatory effects on SFMC, suggesting that IL-10 may be useful in the treatment of patients with RA.

Revue / Journal Title

Arthritis and rheumatism   ISSN 0004-3591   CODEN ARHEAW 

Source / Source

1996, vol. 39, n^o3, pp. 386-395 (47 ref.)

Langue / Language

Anglais

Editeur / Publisher

Wiley, Hoboken , NJ, ETATS-UNIS  (1958) (Revue)

Mots-clés anglais / English Keywords

Rheumatoid arthritis ; Interleukin 10 ; Biological effect ; Phenotype ; Mononuclear cell ; Synovial fluid ; Antiinflammatory agent ; Immunomodulator ; Human ; Chronic ; Diseases of the osteoarticular system ; Inflammatory joint disease ; Immunopathology ; Autoimmune disease ;

Mots-clés français / French Keywords

Polyarthrite rhumatoïde ; Interleukine 10 ; Effet biologique ; Phénotype ; Mononucléaire ; Liquide synovial ; Antiinflammatoire ; Immunomodulateur ; Homme ; Chronique ; Système ostéoarticulaire pathologie ; Rhumatisme inflammatoire ; Immunopathologie ; Maladie autoimmune ;

Mots-clés espagnols / Spanish Keywords

Poliartritis reumatoidea ; Interleuquina 10 ; Efecto biológico ; Fenotipo ; Mononuclear ; Líquido sinovial ; Antiinflamatorio ; Inmunomodulador ; Hombre ; Crónico ; Sistema osteoarticular patología ; Reumatismo inflamatorio ; Inmunopatología ; Enfermedad autoinmune ;

Localisation / Location

INIST-CNRS, Cote INIST : 8711, 35400004499258.0050