Inhibitors of Tumor Necrosis Factor Synthesis as a New Appro | 54895

Журнал артрита

ISSN - 2167-7921


Inhibitors of Tumor Necrosis Factor Synthesis as a New Approach for the Treatment of Rheumatoid Arthritis

Mariana Trivilin Mendes, Rafaela Fadoni Alponti, Patrícia Lucio Alves, Isabela Lopes Trevizan, Regina Pekelmann Markus, Pedro Augusto Fernandes, Paulo Flávio Silveira

Objective: The treatment of rheumatoid arthritis (RA) is based on the inhibition
of TNF. Here we evaluated whether drugs that might inhibit TNF, such as
pentoxifylline (PTX), rupatadine (RUP), rolipram (ROL) and thalidomide (THA),
could be an alternative for RA treatment.
Methods: In wistar male rats the changes in paw thickness, plasma TNF and
by the activity of basic aminopeptidase (APB) in soluble fraction of synovial
tissue and peripheral blood mononuclear cells (PBMC) evaluated after
daily injection for 30 days were taken as anti-inflammatory outputs, while
hepatotoxicity was assessed by measuring plasma alanine transaminase
(ALT) and aspartate transaminase (AST) activity. The content of IL1-, IL-6
in serum and synovial fluid and the histology of the injured tissue were
determined only for ROL, THA and ROL+THA. Prednisolone was used as a
standard drug.
Results: Collagen treatment induced paw thickness, histological changes in
the tibiotarsal joint, increase in synovial fluid of both cytokines and synovial
tissue of APB activity. Furthermore, the APB activity in PBMC was reduced
and ALT and AST activity were enhanced. The most effective drug schedule
in reducing arthritis induced changes described above, as well as recovering
from control levels TNF, IL1-β, APB in synovial tissue and AST activities were
THA and the association of ROL and THA. However, only THA alone reduced
the levels of ALT.
Conclusion: The synthesis of TNF in RA models can be blocked by drugs acting
at different targets. We show that THA and THA+ROL emerges as simple and
effective therapeutic alternatives for RA.