Dynamics of blood components and peritoneal fluid during treatment of murine E. coli sepsis with beta-1,3-D-polyglucose derivatives. II. Interleukin 1, tumour necrosis factor, prostaglandin E2, and leukotriene B4.
The influences of pretreatment with beta-1,3-D-polyglucose derivatives on levels of cytokines and arachidonic acid metabolites in body fluids in experimental peritonitis in mice are reported. Peritonitis was induced by an intraperitoneal injection of 10(8) live Escherichia coli. Pretreated animals survived the infection, untreated animals died about 12 h after inoculation with E. coli. Levels of IL-1 in plasma and peritoneal fluid, measured by cytotoxicity assay of the HT-2 cell line, increased significantly during the first 48 h after intraperitoneal treatment with beta-1,3-D-polyglucose-derivatized microbeads (GDM) or soluble, aminated beta-1,3-D-polyglucose (AG). After subsequent challenge with E. coli, the levels of IL-1 were significantly lower than in untreated animals. There was no increase in levels of TNF after treatment with GDM or AG, measured by cytotoxicity assay of the WEHI clone 13 cell line. After challenge with E. coli, TNF in plasma and peritoneal fluid was significantly lower compared with untreated animals. Both PGE2 and LTB4, measured by radioimmunoassay kits, were increased in peritoneal fluid after treatment with GDM and AG. After challenge with E. coli, PGE2 and LTB4 in peritoneal fluid increased to about half the concentration of infected control animals. Intraperitoneal injection of indomethacin to pretreated animals resulted in increased levels of IL-1 and TNF and decreased levels of PGE2 following challenge with E. coli. The levels of IL-1 and TNF remained elevated until the animals died after about 12 h. These studies demonstrate that the raised levels of arachidonic acid metabolites after pretreatment with GDM or AG seem to inhibit the otherwise lethal elevation of IL-1 and TNF in body fluids which is seen in untreated animals.
Rasmussen
L T
LT
Institute of Medical Biology, University of Tromsø, Norway.
Fandrem
J
J
Seljelid
R
R
D000818:Animals; D001095:Arachidonic Acids / Q000097:blood*; D001202:Ascitic Fluid / Q000276:immunology*; D016207:Cytokines / Q000097:blood*; D015232:Dinoprostone / Q000097:blood; D004927:Escherichia coli Infections / Q000097:blood / Q000276:immunology* / Q000517:prevention & control; D005260:Female; D005936:Glucans / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000097:blood; D007958:Leukocyte Count / Q000187:drug effects; D007975:Leukotriene B4 / Q000097:blood; D051379:Mice; D008808:Mice, Inbred CBA; D018805:Sepsis / Q000097:blood / Q000276:immunology* / Q000517:prevention & control; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D047071:beta-Glucans
D001095:Arachidonic Acids; D016207:Cytokines; D005936:Glucans; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D047071:beta-Glucans; D007975:Leukotriene B4; C033363:beta-1,3-glucan; D015232:Dinoprostone; D007213:Indomethacin