PMID- 1599496
OWN - NLM
STAT- MEDLINE
DCOM- 19920708
LR  - 20190623
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 43
IP  - 10
DP  - 1992 May 28
TI  - Time course of various inflammatory mediators during recurrent endotoxemia.
PG  - 2103-9
AB  - The time course of thromboxane B2 (TxB2), 6-keto-PGF1 alpha (stable metabolite of 
      prostacyclin), tumor necrosis factor-alpha (TNF alpha), platelet activating 
      factor (PAF), and interleukin-6 (IL-6) formation after three lipopolysaccharide 
      (LPS) infusions was studied in pigs over an 18-hr, period. The Escherichia coli 
      endotoxin W0111:B4 was injected i.v. into 10 of the test group pigs at a dose of 
      0.5 micrograms/kg over 30 min at 0, 5 and 10 hr of the experiment. Three pigs 
      injected with physiological saline served as controls. At defined time points 
      before and after each LPS administration venous blood was withdrawn (0, 15, 30, 
      45, 60, 120, 180 min) and plasma levels of TxB2, 6-keto-PGF 1 alpha, PAF, TNF 
      alpha and IL-6 were determined. Pulmonary artery pressure (PAP) and cardiac 
      output (CO) were measured every 15 min. TxB2 and PAF peaked significantly between 
      30 and 45 min, TNF alpha and 6-keto-PGF 1 alpha between 30 and 60 min, and IL-6 
      between 120 and 180 min after each LPS injection. The mediators PAF, TNF alpha 
      and TxB2 showed a decreasing three-peak profile whereas 6-keto-PGF1 alpha 
      exhibited an increasing one. IL-6 plasma concentrations increased after each LPS 
      injection. The peak after the third LPS administration, however, was surprisingly 
      low compared to the previous two. The first LPS infusion in our test group led to 
      a significant, sustained rise in mean PAP. After recurrent LPS injections the 
      peak in PAP was not as marked as after the first infusion, indicating the 
      development of a tolerance towards LPS. Initially, CO showed hypodynamic values, 
      whereas the end stage of the experiment was characterized by hyperdynamic CO 
      levels. In conclusion, we believe this porcine model of septic shock to be one of 
      the first large animal models to describe in detail the time-course of various 
      important inflammatory mediators.
FAU - Klosterhalfen, B
AU  - Klosterhalfen B
AD  - Department of Pathology, Technical University of Aachen, Federal Republic of 
      Germany.
FAU - Horstmann-Jungemann, K
AU  - Horstmann-Jungemann K
FAU - Vogel, P
AU  - Vogel P
FAU - Flohe, S
AU  - Flohe S
FAU - Offner, F
AU  - Offner F
FAU - Kirkpatrick, C J
AU  - Kirkpatrick CJ
FAU - Heinrich, P C
AU  - Heinrich PC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Interleukin-6)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Platelet Activating Factor)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 54397-85-2 (Thromboxane B2)
RN  - 58962-34-8 (6-Ketoprostaglandin F1 alpha)
SB  - IM
MH  - 6-Ketoprostaglandin F1 alpha/blood
MH  - Animals
MH  - Inflammation/metabolism
MH  - Interleukin-6/blood
MH  - Lipopolysaccharides
MH  - Platelet Activating Factor/*analysis
MH  - Pulmonary Wedge Pressure
MH  - Shock, Septic/chemically induced/*metabolism
MH  - Swine
MH  - Thromboxane B2/*blood
MH  - Time Factors
MH  - Tumor Necrosis Factor-alpha/*analysis
EDAT- 1992/05/28 00:00
MHDA- 1992/05/28 00:01
CRDT- 1992/05/28 00:00
PHST- 1992/05/28 00:00 [pubmed]
PHST- 1992/05/28 00:01 [medline]
PHST- 1992/05/28 00:00 [entrez]
AID - 0006-2952(92)90167-H [pii]
AID - 10.1016/0006-2952(92)90167-h [doi]
PST - ppublish
SO  - Biochem Pharmacol. 1992 May 28;43(10):2103-9. doi: 10.1016/0006-2952(92)90167-h.