Combined atorvastatin and pentoxifylline in ameliorating inflammation induced by complete Freund’s adjuvant

Injection of complete Freund’s adjuvant (CFA) into one of the footpads of Wistar rats promotes swelling in all the footpads (including non-injected footpads) in the next few days, indicating a complicated immunological reaction and autoimmune arthritis. This survey was performed to assess the synergistic benefits of combined atorvastatin and pentoxifylline for treating arthritis induced by CFA. Therapeutic regimes began on day 12 post-challenge when all the rats recorded an arthritis index of more than one and continued throughout the investigation until day 32. Treatment with combined atorvastatin and pentoxifylline at half doses led to synergistic benefits causing the regression of clinical and radiological appearance of arthritis in non-injected paws, which was more favorable than treatment with any medication alone at full doses. Moreover, the combined treatment led to a reduction in some inflammatory biochemical parameters, such as myeloperoxidase, nitric oxide, and C-reactive protein, which was more pronounced than those of the treatment with each medication alone. The mRNA expression of IL-1β and TNF-α in the rat toe area was significantly decreased by combination therapy, and this reduction was more significant than that of monotherapy. The ratios of RORγc/T-bet, RORγc/GATA-3, RoRγc/Foxp3, T-bet/GATA-3, and T-bet/Foxp3 expression showed a further decrease in the combined treated group compared to other groups. Interestingly, combination therapy did not reduce T lymphocyte proliferation to a level lower than healthy rats. Overall, the combination of atorvastatin and pentoxifylline possesses immunomodulatory synergistic benefits, and this approach may be an impressive strategy to manage complicated inflammation.