Protective effect of anisodamine against Shiga toxin-1: Inhibition of cytokine production and increase in the survival of mice

Abstract

The purpose of this study was to investigate whether anisodamine could inhibit Shiga toxin-1 (Stx1)-induced cytokine production and increase the survival of Stx1-treated mice. Human monocytic cells were stimulated by Stx1 (1 to 100 ng/mL) with or without anisodamine addition (1 to 400 μg/mL). For in vivo evaluations, C57BL/6 mice were given a single intraperitoneal injection of anisodamine (1 mg) or saline solution after intraperitoneal injection of Stx1 (2.75 μg/kg). The results showed that anisodamine significantly suppressed Stx1-induced tumor necrosis factor-α (TNF-α), interleuking-1β (IL-1β), and IL-8 production. Reverse transcriptase–polymerase chain reaction (RT-PCR) showed that anisodamine suppressed Stx1-mediated TNF-α mRNA expression. Further study showed that this TNF-α inhibitory effect was via a prostaglandin E2–dependent mechanism. Anisodamine treatment prolonged the survival time of mice and decreased the lethality of Stx1 (94.5% to 44%). Because cytokines, in particular TNF-α, contribute to the pathologic process in Stx-producing Escherichia coli (STEC) infection, this study suggested that anisodamine could be a potential drug for treatment of STEC infection. (J Lab Clin Med 2001;137:93-100)