Inflammatory cytokines in an experimental model for the multiple organ dysfunction syndrome.
OBJECTIVE
To investigate the alterations in circulating pro-inflammatory cytokines and cytokine production by peritoneal macrophages during the development of multiple organ dysfunction syndrome.


METHODS
Prospective, controlled laboratory study on zymosan-induced generalized inflammation in mice. Single intraperitoneal administration of zymosan induces, over a 12-day period, a triphasic illness in mice; the third phase, from day 6 onward, resembles multiple organ dysfunction syndrome.


METHODS
Animal research laboratory.


METHODS
C57BL/6CRW mice received a single intraperitoneal dose of zymosan on day 0, and standard numbers of animals were killed at different time points up until day 12.


RESULTS
Plasma concentrations of interleukin (IL)-1 alpha and IL-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha were measured from 3 hrs to 12 days after administration of zymosan. At the same time points, both lipopolysaccharide-stimulated and unstimulated production of these cytokines by peritoneal macrophages were measured in vitro. Plasma TNF and IL-6 concentrations transiently increased during the first 24 hrs after administration of zymosan. After 8 days, a prominent peak of biologically inactive TNF was observed. Both unstimulated and lipopolysaccharide-stimulated cytokine production by peritoneal cells showed profound changes during the experimental period.


CONCLUSIONS
These findings seem to confirm our hypothesis that the macrophages are in a continuously activated state and altered in their function, when the animals develop multiple organ dysfunction syndrome. Further studies are needed to elucidate what happens with these cytokines at the tissue level, to better understand the pathophysiology of multiple organ dysfunction syndrome.
Jansen
M J
MJ
Department of Surgery, university Hospital Nijmegen, The Netherlands.
Hendriks
T
T
Vogels
M T
MT
van der Meer
J W
JW
Goris
R J
RJ
D000818:Animals; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D004195:Disease Models, Animal; D066298:In Vitro Techniques; D007249:Inflammation / Q000378:metabolism; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009102:Multiple Organ Failure / Q000097:blood / Q000139:chemically induced / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015054:Zymosan
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D015054:Zymosan