Peptidoglycan of Staphylococcus aureus causes inflammation and organ injury in the rat.
OBJECTIVE
Previous studies have implicated a role of peptidoglycan in the pathophysiology of organ injury in sepsis. However, the systemic response to, and organ injury caused by, peptidoglycan have been scarcely studied in vivo.


METHODS
Prospective, randomized study.


METHODS
University-based research laboratory.


METHODS
Fifty-seven anesthetized, male Wistar rats.


METHODS
After surgical preparation, anaesthetized rats were administered 3 mg/kg Staphylococcus aureus peptidoglycan (n = 9), 10 mg/kg S. aureus peptidoglycan (n = 14), or an equal volume of saline (sham, n = 12) in the jugular vein over a 10-min period.


RESULTS
Injection of low-dose peptidoglycan (3 mg/kg) had no measurable effects on the rats. In contrast, high-dose peptidoglycan (10 mg/kg) caused increased serum values of aspartate aminotransferase (p < or =.005), alanine aminotransferase (p < or =.001), gamma-glutamyltransferase, and bilirubin (p < or =.05) (indicators of liver injury/dysfunction) as well as a moderate, but significant, increase in serum creatinine and urea (p < or =.05) (indicators of renal dysfunction). Plasma analyses showed a substantial increase in plasma values of tumor necrosis factor-alpha, interleukin-6, and interleukin-10 (p < or =.05 for all vs. sham) at 1 and 3 hrs (enzyme-linked immunosorbent assay). This was accompanied by accumulation of messenger RNAs for tumor necrosis factor-alpha, interleukin-6, and interleukin-10 in both the liver and the lung (p < or =.05 for all cytokines vs. sham) (real-time polymerase chain reaction). Peptidoglycan also caused increased DNA binding of nuclear factor-kappaB (band-shift assays) and phosphorylation of c-Jun and Jun N-terminal kinase (Western blots). In the kidney, interleukin-6 messenger RNA was increased, whereas Toll-like receptor 4 messenger RNA was significantly decreased.


CONCLUSIONS
These results demonstrate that injection of peptidoglycan alone causes organ injury/dysfunction, organ inflammation, and systemic inflammation in the rat, involving nuclear factor-kappaB and possibly activator protein 1. These data support the contention that peptidoglycan is a contributing factor in the pathophysiology of organ injury in sepsis.
Wang
Jacob E
JE
William Harvey Research Institute, Qeen Mary University of London, UK.
Dahle
Maria K
MK
Yndestad
Arne
A
Bauer
Inge
I
McDonald
Michelle C
MC
Aukrust
Pål
P
Foster
Simon J
SJ
Bauer
Michael
M
Aasen
Ansgar O
AO
Thiemermann
Christoph
C
D000818:Animals; D007249:Inflammation / Q000209:etiology*; D008297:Male; D009102:Multiple Organ Failure / Q000209:etiology*; D010457:Peptidoglycan / Q000008:administration & dosage; D011446:Prospective Studies; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013211:Staphylococcus aureus
D010457:Peptidoglycan