Enhanced in vitro induced production of interleukin 10 by peripheral blood mononuclear cells in rheumatoid arthritis is associated with clinical response to methotrexate treatment.
OBJECTIVE
To investigate the effect of in vivo treatment with methotrexate (MTX) on the regulation of ex vivo interleukin 10 (IL-10) production by peripheral blood mononuclear cells (PBMC) derived from patients with rheumatoid arthritis (RA).


METHODS
Spontaneous as well as lipopolysaccharide (LPS) and phytohemagglutinin (PHA) induced IL-10 release was assessed by a specific immunoassay in culture supernatants of PBMC derived from 32 patients with active RA before and 6, 12, and 24 weeks after MTX treatment. IL- 10 production was correlated to the clinical response. As a control, IL-10 release from PBMC of 7 healthy blood donors was determined.


RESULTS
PBMC of patients with RA showing > 50% improvement of the Paulus index after 3 and 6 months of MTX treatment (responders; n = 18) exhibited significantly enhanced IL-10 production after in vitro stimulation with LPS, whereas constitutively released IL-10 was below the detection limit of the immunoassay in all patients and controls. In contrast, IL-10 release from LPS stimulated PBMC of RA patients who showed < 20% improvement by Paulus index (nonresponders; n = 14) or who even deteriorated compared to baseline disease activity was markedly downregulated during MTX treatment in vivo. PHA-induced IL-10 release from PBMC in vitro was not significantly affected by MTX in vivo whether RA patients responded or not to MTX.


CONCLUSIONS
Enhanced ex vivo LPS induced IL-10 production by PBMC of patients with RA is associated with a favorable therapeutic response to MTX treatment, whereas reduced production coincides more closely with disease deterioration or insufficient response. This may reflect both disease outcome upon treatment and/or the mode of the antiinflammatory action of MTX in RA. Because the LPS--but not the PHA--induced ex vivo IL-10 production by PBMC was stimulated by MTX in vivo, monocytes seem to be the prominent target cells for this drug mediated antiinflammatory cytokine regulation.
Seitz
M
M
Department of Rheumatology and Clinical Immunology/Allergology, University Hospital, Inselspital, Bern, Switzerland. michael.seitz@insel.ch
Zwicker
M
M
Wider
B
B
D000328:Adult; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D001799:Blood Sedimentation; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D012189:Retrospective Studies; D016896:Treatment Outcome
D018501:Antirheumatic Agents; D008070:Lipopolysaccharides; D010835:Phytohemagglutinins; D016753:Interleukin-10; D008727:Methotrexate