PRO-INFLAMMATORY SIGNAL DELIVERED IN
VITRO BY LEFLUNOMIDE ACTIVE METABOLITE
A77 1726 ON ABNORMAL PERIPHERAL
MONOCYTES IN RHEUMATOID ARTHRITIS.
LĂCRĂMIOARA POPA1, CAROLINA NEGREI1, IONELA
VICTORIA NEAGOE2, LUCIAN ALBULESCU2, VASILE
PREOTEASA2, ANDRA RODICA BĂLĂNESCU1, MIHAELA
VIOLETA GHICA1, GINA MANDA2*
1 University of Medicine and Pharmacy “Carol Davila”, Faculty of
Pharmacy, 6 Traian Vuia str., 020956 Bucharest, Romania
2 “Victor Babeş” National Institute of Pathology, 99-101 Splaiul
Independenţei str., 050096 Bucharest, Romania
*corresponding author: gina.manda@gmail.com
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Abstract:

We investigated the effects exerted in vitro by leflunomide active metabolite
A77 1726 and methotrexate (MTX) on cytokine release by monocytes from rheumatoid arthritis patients. Our results give insight information about the action mode of A77 1726 on excessively numerous, activated peripheral monocytes from rheumatoid arthritis patients which do not respond to the current therapy. We highlight that low concentrations of A77 1726 may exert in vitro a pro-inflammatory effect by sustaining the release of proinflammatory factors by such abnormal peripheral monocytes (tumor necrosis factor-α - TNFα, granulocyte macrophage colony-stimulating factor - GM-CSF and interleukin-8 - IL-8). This is a direct action of A77 1726, which is not related to a significant disturbance of pyrimidine metabolism. We showed that MTX can also sustain in vitro the release of GM-CSF. Accordingly, our study points out that in particular circumstances, such as a high number of activated peripheral monocytes subjected to low concentrations of drugs, A77 1726 and to a lesser extent MTX, may sustain the systemic inflammatory process in rheumatoid arthritis.

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