Methotrexate therapy in rheumatoid arthritis patients diminishes lectin-induced mononuclear cell proliferation.
Methotrexate (MTX) is an anti-folate drug used in cancer chemotherapy because of its anti-proliferative effects. However, it is unclear whether the anti-proliferative effects of MTX contribute to the efficacy of low-dose MTX in the treatment of rheumatoid arthritis (RA). To date, either no change or a paradoxical increase in lectin-induced proliferation has been observed in cultures of peripheral blood mononuclear cells (PBMC) from MTX-treated RA patients (RA + MTX). In these earlier studies, high folate-containing media and tritiated thymidine (3H-TdR) were used. Our studies were designed to test the hypothesis that the use of a culture medium with a low folate content along with tritiated deoxyuridine (3H-UdR) permits detection of diminished phytohemagglutinin (PHA)-induced proliferative responses of PBMC from RA + MTX. The data demonstrate decreased PHA-induced cellular proliferation of cultured PBMC from RA + MTX compared with controls. When comparing the PBMC proliferative responses in high vs low folate medium, a significantly greater increase (P less than 0.05) in proliferation occurs in the cells from RA + MTX cultured in the high folate medium. This suggests that an in vivo folate-deficient state of the cells from RA + MTX may be corrected in vitro when a high folate medium is used in culture. We conclude that the use of 3H-UdR and a medium containing folate within the normal range of plasma folate levels eliminates artifacts associated with the use of high folate medium and 3H-TdR, which obscures the anti-proliferative effect of MTX in RA patients.
Hine
R J
RJ
Department of Nutrition Sciences, University of Alabama, Birmingham 35294.
Everson
M P
MP
Hardin
J M
JM
Morgan
S L
SL
Alarcòn
G S
GS
Baggott
J E
JE
Koopman
W J
WJ
Krumdieck
C L
CL
D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media / Q000737:chemistry / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D003857:Deoxyuridine / Q000378:metabolism; D005260:Female; D005492:Folic Acid / Q000032:analysis / Q000494:pharmacology; D006801:Humans; D037102:Lectins / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000187:drug effects; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D003470:Culture Media; D037102:Lectins; D010835:Phytohemagglutinins; D014316:Tritium; D004247:DNA; D005492:Folic Acid; D013936:Thymidine; D003857:Deoxyuridine; D008727:Methotrexate