Document Detail


Iron dysregulation combined with aging prevents sepsis-induced apoptosis.
MedLine Citation:
PMID:  15921699     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Sepsis, iron loading, and aging cause independent increases in gut epithelial and splenic apoptosis. It is unknown how their combination will affect apoptosis and systemic cytokine levels.
MATERIALS AND METHODS: Hfe-/- mice (a murine homologue of hemochromatosis) abnormally accumulate iron in their tissues. Aged (24-26 months) or mature (16-18 months) Hfe-/- mice and wild type (WT) littermates were subjected to cecal ligation and puncture (CLP) or sham laparotomy. Intestine, spleen, and blood were harvested 24 h later and assessed for apoptosis and cytokine levels.
RESULTS: Gut epithelial and splenic apoptosis were low in both aged septic and sham Hfe-/- mice, regardless of the amount of iron in their diet. Mature septic WT mice had increased apoptosis compared to age-matched sham WT mice. Mature septic Hfe-/- mice had similar levels of intestinal cell death to age-matched septic WT mice but higher levels of splenic apoptosis. Apoptosis was significantly lower in septic aged Hfe-/- mice than septic mature Hfe-/- animals. Interleukin-6 was elevated in septic aged Hfe-/- mice compared to sham mice.
CONCLUSIONS: Although sepsis, chronic iron dysregulation, and aging each increase gut and splenic apoptosis, their combination yields cell death levels similar to sham animals despite the fact that aged Hfe-/- mice are able to mount an inflammatory response following CLP and mature Hfe-/- mice have elevated sepsis-induced apoptosis. Combining sepsis with two risk factors that ordinarily increase cell death and increase mortality in CLP yields an apoptotic response that could not have been predicted based upon each element in isolation.
Authors:
Pardis Javadi; Timothy G Buchman; Paul E Stromberg; Isaiah R Turnbull; Dinesh Vyas; Richard S Hotchkiss; Irene E Karl; Craig M Coopersmith
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of surgical research     Volume:  128     ISSN:  0022-4804     ISO Abbreviation:  J. Surg. Res.     Publication Date:  2005 Sep 
Date Detail:
Created Date:  2005-08-23     Completed Date:  2005-10-20     Revised Date:  2014-09-16    
Medline Journal Info:
Nlm Unique ID:  0376340     Medline TA:  J Surg Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  37-44     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Aging / physiology*
Animals
Apoptosis / physiology*
Chronic Disease
Female
Iron Metabolism Disorders / physiopathology*
Male
Mice
Sepsis / physiopathology*
Grant Support
ID/Acronym/Agency:
GM 44118/GM/NIGMS NIH HHS; GM 55194/GM/NIGMS NIH HHS; GM 66202/GM/NIGMS NIH HHS; GM00709/GM/NIGMS NIH HHS; GM08795/GM/NIGMS NIH HHS; GM48095/GM/NIGMS NIH HHS; K08 GM000709/GM/NIGMS NIH HHS; P30 DK52574/DK/NIDDK NIH HHS; R01 GM066202/GM/NIGMS NIH HHS
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