Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving cannabinoid receptor CB2.

BACKGROUND: Recent evidence has shown that the antimalarials are useful drugs in the treatment of various rheumatic diseases. The present study was designed to test the therapeutic effect of pyrimethamine (PYR) in collagen-induced arthritis (CIA).

MATERIAL/METHODS: CIA was induced in Lewis rats. The intraperitoneal administration of PYR and methotrexate (MTX) were started on day 25 post-immunization and continued until final assessment on day 35. During this period, clinical examination was performed intermittently. Anti-C II Ab and nitric oxide (NO) synthesis were measured. The paws and knees were then removed for histopathology and radiography assay. The biocompatibility of PYR and MTX were assessed using a fibrosarcoma cell line.

RESULTS: Data showed that i.p. injection of pyrimethamine to arthritic rats induced a significant reduction in paw edema. This beneficial effect was associated with a significant decrease in anti-CII antibody response compared with untreated rats. Histopathological assessment showed reduced inflammatory cell infiltrate in the joints of treated rats, and tissue edema and bone erosion in the paws were markedly reduced following PYR therapy. Moreover, our radiography results paralleled our histological findings. Cytotoxicity analysis of PYR showed greater tolerability compared with MTX. Treatment with PYR significantly diminished nitric oxide formation in treated rats compared with untreated controls.

CONCLUSIONS: Our findings shed light on the therapeutic efficacy of pyrimethamine in experimental rheumatoid arthritis compared with a choice drug (methotrexate), which may recommended it as a second-line drug in the treatment of rheumatoid arthritis.