Colchicine has Dose-Dependent Therapeutic Effects in a LPS-Induced Experimental Endotoxemia Model

Abstract

Colchicine is an ancient medication that has long been used for anti-inflammatory properties. Because of unfavorable and toxic consequences of colchicine, selecting an appropriate dose is critical. The effects of three different doses (0.5, 1 or 5 mg/kg) of colchicine were evaluated. To stimulate systemic inflammation, we created an LPS-induced experimental endotoxemia model with 1 mg/kg LPS intraperitoneal injection. Possible therapeutic effects of colchicine were investigated on cytokines, decreased mesenteric artery blood flow and histopathological damage scores. Treatment with 1 mg/kg colchicine reduced the pro-inflammatory cytokines IL-1β, TNF-α, IL-8, and IL-17 to levels comparable to the control group and attenuated the damage caused by LPS in liver and spleen tissues. At a dose of 0.5 mg/kg, colchicine was not able to decrease cytokine levels to those of the control group. In contrast, administration of 5 mg/kg colchicine ameliorated mesenteric blood flow; however, this higher dose caused an increase in cytokine levels. Among three different colchicine doses, 1 mg/kg intraperitoneal dose significantly improved the inflammatory indices and may be considered a suitable option for anti-inflammatory treatment.

Keywords: LPS‐induced endotoxemia; anti‐inflammatory effect; colchicine; mesenteric artery blood flow; multiple organ damage.