Rheumatology International

, Volume 10, Issue 4, pp 165–169 | Cite as

Methotrexate therapy in rheumatoid arthritis patients diminishes lectin-induced mononuclear cell proliferation

  • R. J. Hine
  • M. P. Everson
  • J. M. Hardin
  • S. L. Morgan
  • G. S. Alarcòn
  • J. E. Baggott
  • W. J. Koopman
  • C. L. Krumdieck


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<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 of3H-UdR and a medium containing folate within the normal range of plasma folate levels eliminates artifacts associated with the use of high folate medium and3H-TdR, which obscures the anti-proliferative effect of MTX in RA patients.

Key words

Methotrexate Rheumatoid arthritis Folate Anti-proliferative 


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Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • R. J. Hine
    • 1
  • M. P. Everson
    • 2
    • 4
  • J. M. Hardin
    • 3
  • S. L. Morgan
    • 1
  • G. S. Alarcòn
    • 2
    • 4
  • J. E. Baggott
    • 1
  • W. J. Koopman
    • 2
    • 4
  • C. L. Krumdieck
    • 1
  1. 1.Department of Nutrition Sciences, Clinical Nutrition Research UnitThe University of Alabama at Birmingham (UAB)BirminghamUSA
  2. 2.Department of Medicine, Division of Clinical Immunology and RheumatologyThe University of Alabama at Birmingham (UAB)BirminghamUSA
  3. 3.Department of Biostatistics and Biomathematics and Comprehensive Cancer CenterThe University of Alabama at Birmingham (UAB)BirminghamUSA
  4. 4.Veterans Administration Medical CenterBirminghamUSA

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