This Article  • References  • Full text PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Social Bookmarking   What's this?

Alfred Ayala, PhD; Zoe K. Deol, MD; Donna L. Lehman; Crystal D. Herdon; Irshad H. Chaudry, PhD

Arch Surg. 1995;130(11):1178-1185.

Abstract
Background
Endotoxin (ETX) is thought to be the primary inducer of proinflammatory mediator release associated with bacterial sepsis. Furthermore, a number of studies indicate that preexposure of animals to high doses of ETX produces macrophages (Møs) that are refractory to ex vivo stimulation with ETX. However, it is unknown if levels of ETX comparable to those typically encountered in sepsis induce a similar refractory state in Møs.

Design
To assess this, peritoneal Møs (PMøs) were harvested from C3H/HeN mice (ETX sensitive) at 1 hour (early) or 24 hours (late) following cecal ligation and puncture (CLP) to induce polymicrobial sepsis, sham CLP, or laparotomy followed by peritoneal implantation of a minipump delivering either saline or ETX (0.025 µg/g of body weight, every 24 hours). Peritoneal Mø cultures were incubated with ETX, either 0 or 10 µg/mL, for 24 hours, and their ability to release interleukin-1, interleukin-6, and tumor necrosis factor was assessed by bioassay.

Results
Chronic low-dose ETX with 0 µg of ETX media added produced early (at 1 hour) in vivo activation of PMø interleukin-1 release, which was comparable to that seen in mice subjected to CLP. However, unlike PMøs taken from CLP mice, PMøs from mice implanted with the ETX minipump at 1 or 24 hours showed no marked decline in their ability to respond to ETX (10 µg). Comparable changes were seen for interleukin-6 and tumor necrosis factor release.

Conclusions
Bacterial component(s) other than ETX per se induces the sustained dysfunction in PMø capacity to produce proinflammatory cytokines during sepsis and/or peritonitis. Thus, agents directed against ETX alone may not be adequate in the treatment of polymicrobial sepsis.

(Arch Surg. 1995;130:1178-1185)

Author Affiliations
From the Departments of Surgery (Drs Ayala, Deol, and Chaudry and Mss Lehman and Herdon), Microbiology (Dr Ayala), and Physiology (Dr Chaudry), Shock and Trauma Institute, Michigan State University, East Lansing.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

PD-1 expression by macrophages plays a pathologic role in altering microbial clearance and the innate inflammatory response to sepsis
Huang et al.
Proc. Natl. Acad. Sci. USA 2009;106:6303-6308.
ABSTRACT | FULL TEXT  

Supplementation of {Omega}-3 Fatty Acids in Parenteral Nutrition Beneficially Alters Phospholipid Fatty Acid Pattern
Senkal et al.
JPEN J Parenter Enteral Nutr 2007;31:12-17.
ABSTRACT | FULL TEXT  

Sepsis-induced SOCS-3 expression is immunologically restricted to phagocytes
Grutkoski et al.
J. Leukoc. Biol. 2003;74:916-922.
ABSTRACT | FULL TEXT  

Effects of Calorie Restriction on Polymicrobial Peritonitis Induced by Cecum Ligation and Puncture in Young C57BL/6 Mice
Sun et al.
CVI 2001;8:1003-1011.
ABSTRACT | FULL TEXT  

MAPK p38 antagonism as a novel method of inhibiting lymphoid immune suppression in polymicrobial sepsis
Song et al.
Am. J. Physiol. Cell Physiol. 2001;281:C662-C669.
ABSTRACT | FULL TEXT  

The Pivotal Role of Adrenomedullin in Producing Hyperdynamic Circulation During the Early Stage of Sepsis
Wang et al.
Arch Surg 1998;133:1298-1304.
ABSTRACT | FULL TEXT