Enhanced in vitro induced production of interleukin 10 by peripheral bloodmononuclear 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 pe ripheral blood mononuclear cells (PBMC) derived from patients with rheumato id arthritis (RA). Methods. Spontaneous as well as lipopolysaccharide (LPS) and phytohemagglut inin (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 correlat ed to the clinical response. As a control, IL-10 release from PBMC of 7 hea lthy blood donors was determined. Results. PBMC of patients with RA showing > 50% improvement of the Paulus i ndex after 3 and 6 months of MTX treatment (responders; n = 18) exhibited s ignificantly 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 i ndex (nonresponders; n = 14) or who even deteriorated compared to baseline disease activity was markedly downregulated during MTX treatment in vivo. P HA-induced IL-10 release from PBMC in vitro was not significantly affected by MTX in vivo whether RA patients responded or not to MTX. Conclusion. Enhanced ex vivo LPS induced IL-10 production by PBMC of patien ts with RA is associated with a favorable therapeutic response to MTX treat ment, whereas reduced production coincides more closely with disease deteri oration or insufficient response. This may reflect both disease outcome upo n treatment and/or the mode of the antiinflammatory action of MTX in RA. Be cause the LPS - but not the PNA - induced ex vivo IL-10 production by PBMC was stimulated by MTX in vivo, monocytes seem to be the prominent target ce lls for this drug mediated antiinflammatory cytokine regulation.