IMMUNOMODULATORY EFFECTS OF METHADONE FOLLOWING
METHOTREXATE THERAPY IN A RAT MODEL OF ARTHRITIS
MARIA BÂRCĂ1, GINA MANDA2, ANNE-MARIE CIOBANU1*, CRISTIAN BĂLĂLĂU3, DUMITRU LUPULEASA1, GEORGE TRAIAN ALEXANDRU BURCEA DRAGOMIROIU1, ANCA POP1, DANIELA ELENA POPA1, DANIELA LUIZA BACONI1
1“Carol Davila” University of Medicine and Pharmacy, Faculty of Pharmacy, 6 Traian Vuia Street, Bucharest, Romania
2“Victor Babeş” National Institute of Pathology, 99 – 101 Splaiul Independenţei Street, Bucharest, Romania
3“Carol Davila” University of Medicine and Pharmacy, Faculty of Medicine, “Sf. Pantelimon” Emergency Hospital, 340 - 342
Pantelimon Avenue, Bucharest, Romania
*corresponding author: anneciobanu@umfcd.ro
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Abstract:
Rheumatoid arthritis (RA) is a chronic autoimmune disease causing inflammation, pain, swelling, stiffness and loss of
function in the joints. The advantage of opioids use in RA treatment is the simultaneous pain control and immune response
modulation. The effects of methadone (MTD) on the proliferation of splenic lymphocytes from Wistar rats treated in vivo
with methotrexate (MTX) after induction of chronic inflammation arthritis were investigated. The animals were administered
three doses of MTX solution for injection and sodium MTX (“hydrosoluble” MTX) or MTX per se (“hydrophobic” MTX)
encapsulated in liposomes. Splenic lymphocytes were activated with concanavaline A and uridine incorporation method was
used for the evaluation of lymphocytes proliferation. The results showed an immunosuppressive effect of MTD in rats treated
with a low dose of MTX (solution for injection or “hydrosoluble” MTX-liposomes) and a persistent inhibition at high doses of
MTX solution for injection. MTD can activate the splenic lymphocytes of animals treated with “hydrophobic” MTX liposomes.
The study indicated that high doses of hydrosoluble and hydrophobic MTX could modulate cells reactivity to MTD.

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