Increased serum endotoxin and elevated CD14 and IL-1beta expression in a rat model of cerebrogenic multiple organ dysfunction syndrome.
OBJECTIVE
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.
Qu
Chuanqiang
C
Department of Neurology, Qilu Hospital, Shandong University, Jinan, 250021, China.
Guo
Shougang
S
Guo
Hongzhi
H
Wang
Chunjuan
C
Ma
Lin
L
He
Yan
Y
Wang
Lei
L
Lou
Jianwei
J
Wang
Xingbang
X
D000818:Animals; D002543:Cerebral Hemorrhage / Q000150:complications; D004195:Disease Models, Animal; D004731:Endotoxins / Q000097:blood*; D005786:Gene Expression Regulation; D053583:Interleukin-1beta / Q000235:genetics*; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D008297:Male; D009102:Multiple Organ Failure / Q000097:blood* / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D055986:Vital Signs
D004731:Endotoxins; D053583:Interleukin-1beta; D018950:Lipopolysaccharide Receptors; D012333:RNA, Messenger