Bupivacaine inhibits COX‐2 expression, PGE₂, and cytokine production in endotoxin‐activated macrophages

Abstract

Background: Upregulation of cyclooxygenase‐2 (COX‐2) and resultant prostaglandin E 2 (PGE 2 ) overproduction has been shown to play a crucial role in initiating a systemic inflammatory response during sepsis. Sepsis also induces robust production of pro‐inflammatory cytokines tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β), and IL‐6 as well as anti‐inflammatory cytokine IL‐10. We sought to elucidate the effects of bupivacaine on COX‐2 expression and production of PGE 2 and cytokines using an endotoxin‐activated murine macrophages model. Methods: Confluent murine macrophages (RAW264.7 cells) were treated with lipopolysaccharide (LPS, 100 ng/ml) or LPS plus bupivacaine (1, 10, or 100 μM). Bupivacaine was added immediately after LPS. After reacting for 18 h, cell cultures were harvested for subsequent analysis. Results: LPS significantly upregulated COX‐2 transcription and PGE 2 production in macrophages. LPS also significantly increased the production of TNF‐α, IL‐1β, IL‐6 and IL‐10 in macrophages. Bupivacaine significantly inhibited the effects of LPS on COX‐2 transcription and PGE 2 production in a dose‐dependent manner. In a dose‐dependent manner, bupivacaine also significantly inhibited the effects of LPS on the production of TNF‐α, IL‐1β, and IL‐6. However, bupivacaine exerted no significant effects on LPS‐induced IL‐10 production. Conclusion: Bupivacaine significantly inhibited COX‐2 expression, PGE 2 and cytokine production in endotoxin‐activated macrophages.