Effect of treatment with methotrexate, hydroxychloroquine, and prednisone on lymphocyte polyamine levels in rheumatoid arthritis: correlation with the clinical response and rheumatoid factor synthesis.
OBJECTIVE
Polyamines are increased in activated lymphocytes, including peripheral blood lymphocytes (PBL) from patients with rheumatoid arthritis (RA), and are important in modulating immune-mediated cellular responses. In vitro studies have suggested that methotrexate (MTX) interferes with polyamine synthesis. This study evaluated the in vivo polyamine response to MTX compared to other anti-arthritic agents, and correlated it with the clinical and immunological response.


METHODS
The polyamine content of PBL was determined in 14 RA patients at initiation of treatment with MTX (n = 8), hydroxychloroquine (HCQ) (n = 3), or prednisone (n = 3), and then monthly for four months. IgM rheumatoid factor (RF) synthesis by PBL in vitro was assessed and tender joints were counted monthly.


RESULTS
Polyamines (spermine and spermidine) decreased by 55% at three months in the MTX group compared to 4% and 9% in the HCQ and prednisone groups, respectively (p < 0.01). However, group differences in the clinical and immunological response were not significant. In the MTX group there was a positive correlation between polyamine levels and the joint count. Such a correlation was not observed in the other groups.


CONCLUSIONS
These data suggest that MTX interference with the polyamine pathway is not shared by prednisone and HCQ, and is associated with its beneficial effect in RA.
Nesher
G
G
Division of Rheumatology, Saint Louis University Health Sciences Center, MO 63104, USA.
Osborn
T G
TG
Moore
T L
TL
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D006886:Hydroxychloroquine / Q000627:therapeutic use; D007596:Joints / Q000473:pathology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D011073:Polyamines / Q000378:metabolism*; D011241:Prednisone / Q000627:therapeutic use; D012217:Rheumatoid Factor / Q000096:biosynthesis*; D012720:Severity of Illness Index
D000893:Anti-Inflammatory Agents; D018501:Antirheumatic Agents; D011073:Polyamines; D006886:Hydroxychloroquine; D012217:Rheumatoid Factor; D011241:Prednisone; D008727:Methotrexate