Background: Autoimmune arthritis is a type of arthritis in which the immune system attacks the body itself. The link between cell death, inflammation and autoimmune diseases has been established, and dysregulation of autophagy has been reported in several autoimmune diseases such as autoimmune arthritis. Simvastatin is a lipid-lowering drug with pleotropic anti-inflammatory and immunomodulatory effects.

Aim of Study: The aim of the present study was to explore the cross-talk between autophagy, necroptosis and metabolic changes in pristane-induced arthritis with highlighting the effect of simvastatin.

Material and Methods: The study was conducted on 50 female mice, which were divided into 5 groups. Group I served as a control; group II was given simvastatin only; group III was given pristane to induce arthritis; group IV was treated with simvastatin from the first day with pristane injection; and group V was treated by simvastatin with the appearance of arthritic manifestations induced by pristane. Joint tissue samples were collected for histopathological examination and biochemical assessment of cholesterol, triacylglycerol and lactate levels using colorimetric techniques, as well as the levels of RIPK3 and Akt using ELISA technique.

Results: Administration of simvastatin from the first day corrected the biochemical changes, induced autophagy, suppressed necroptosis and protected against the arthritic changes. However, the delay in its administration after the appearance of arthritic manifestations resulted in partial improvement. The histopathological findings confirmed the laboratory results.

Conclusion: Simvastatin administration markedly alleviated joint inflammation and damage induced by pristane through inhibition of inflammation, induction of autophagy and suppression of necroptosis. The use of simvastatin as a protective drug against progression of autoimmune arthritis seems to be promising.