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-1beta 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-1beta 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-1beta 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-1beta mRNAs correlated significantly with serum endotoxin levels (Plt;0.01). We conclude that acute cerebral hemorrhage results in endotoxemia and widespread increases in CD14 and IL-1beta expression. We suggest that acute cerebrovascular challenge leads to a stress/shock response that compromises 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.
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-1beta 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-1beta 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-1beta 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-1beta mRNAs correlated significantly with serum endotoxin levels (Plt;0.01). We conclude that acute cerebral hemorrhage results in endotoxemia and widespread increases in CD14 and IL-1beta expression. We suggest that acute cerebrovascular challenge leads to a stress/shock response that compromises 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.