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Pretreatment with interleukin-6 small interfering RNA can improve the survival rate of polymicrobial cecal ligation and puncture mice by down regulating interleukin-6 production

Authors
Mostafa Anower, AK; Shim, JA; Choi, B; Sohn, S
Citation
European journal of pharmacology, 688(1-3):76-83, 2012
Journal Title
European journal of pharmacology
ISSN
0014-29991879-0712
Abstract
Interleukin-6 (IL-6) is considered to be an early marker of severe sepsis that is associated with increased morbidity and mortality. Therefore, we pretreated male ICR mice with IL-6 small interfering RNA (siRNA) before cecal ligation and puncture (CLP) and observed the changes in their survival in response to down regulation of IL-6, as well as the role of Th subsets during sepsis. In addition, sham and CLP operated mice were sacrificed at different time points to determine the serum IL-6 levels during early and late sepsis. IL-6 siRNA pretreated septic mice showed markedly extended survival (23.3%) up to 10 days and significantly reduced serum IL-6 levels at day 5 (209.90 ± 0.50 pg/ml; P<0.0001) when compared to CLP mice at day 1. Furthermore, IL-6 mRNA and protein were highly expressed during early sepsis in CLP mice at day 1 and mRNA was not detected in IL-6 siRNA treated CLP mice at days 1 or 5 and serum level of IL-6 was also decreased significantly (P<0.01). In addition, the mRNA expression of C5aR, ROR-γt, PU.1 and protein expression of IL-17 were high at day 5 in IL-6 siRNA treated mice. Taken together, the results of the present study demonstrate that pretreatment with IL-6 siRNA improved CLP induced septic mice survival. Furthermore, the IL-6 level was down-regulated and the transcription factors ROR-γt and PU.1 were up-regulated by IL-6 siRNA at late sepsis. The results presented herein also suggest that IL-6 siRNA could be a potential molecular therapeutic strategy for the treatment of sepsis.
MeSH terms
Alanine Transaminase/metabolismAnimalsAnti-Bacterial Agents/pharmacologyBlood Urea NitrogenCecum/drug effects/*injuries/*microbiologyDown-Regulation/drug effects/*geneticsInterleukin-6/biosynthesis/*deficiency/*geneticsLigation/adverse effectsMaleMiceMice, Inbred ICRPunctures/*adverse effectsRNA, Small Interfering/*geneticsReceptors, Complement/geneticsSepsis/etiology/metabolism/microbiologySurvival AnalysisSurvival RateT-Lymphocytes, Helper-Inducer/drug effects/metabolismTime Factors
DOI
10.1016/j.ejphar.2012.05.007
PMID
22634167
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Microbiology
AJOU Authors
손, 성향
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