Increased Serum Endotoxin and Elevated CD14 and IL-1β Expression in a Rat Model of Cerebrogenic Multiple Organ Dysfunction Syndrome

Qu      Chuanqiang; Guo      Shougang; Guo      Hongzhi; Wang      Chunjuan; Ma      Lin; He      Yan; Wang      Lei; Lou      Jianwei; Wang      Xingbang

Abstract

Objectives: To study the mechanisms underlying cerebrogenic multiple organ dysfunction syndrome (CMODS) through investigation of endotoxin levels and the expression of endotoxin receptor CD14 and interleukin IL-1β mRNAs in a rat CMODS model. Methods: Acute cerebral hemorrhage was induced in Wistar rats by focal intracerebral injection of collagenase into the caudate nucleus. Serum endotoxin levels were quantitated using a chromogenic limulus lysate method; CD14 endotoxin receptor mRNA and IL-1β mRNA levels in lung and intestine were determined by in situ hybridization. Results: Serum endotoxin levels increased after 12 h, reaching a peak after 24 h, and declined to control levels at 72 h. The increase was statistically significant (P < 0.05) compared to unoperated controls and the sham-operated group respectively. CD14 mRNA in lung and intestine increased after 12 h, peaked after 24-36 h, and then declined after 48 h. IL-1β mRNA levels were also increased in lung and intestine (P < 0.05), peaking at 36 h and declining thereafter. Expression levels of both CD14 and IL-1β mRNAs correlated significantly with serum endotoxin levels (P < 0.01). We conclude that acute cerebral hemorrhage results in endotoxemia and widespread increases in CD14 and IL-1β expression. We suggest that acute cerebrovascular challenge leads to a stress/shock response that compromizes the intestinal mucosal barrier. In turn, this allows endotoxin translocation into the body that provokes the release of pro-inflammatory lymphokines, leading to a systemic inflammatory response syndrome (SIRS) that culminates in multiple organ dysfunction.

Keywords: Multiple organ dysfunctio, endotoxins, CD14, IL-β, gene expression

« Previous Next »