PMID- 8937427
OWN - NLM
STAT- MEDLINE
DCOM- 19970102
LR  - 20190623
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 52
IP  - 8
DP  - 1996 Oct 25
TI  - Influence of heat shock protein 70 and metallothionein induction by 
      zinc-bis-(DL-hydrogenaspartate) on the release of inflammatory mediators in a 
      porcine model of recurrent endotoxemia.
PG  - 1201-10
AB  - The manipulation of stress gene expression by heavy metals provides protection 
      against the lethal effects of endotoxemia in murine models of septic shock. 
      Recent in vitro studies with alveolar macrophages or monocytes show that 
      induction of the stress response in these cells is followed by a decreased 
      liberation of major cytokines [tumor necrosis factor-alpha (TNF alpha) and 
      interleukin-1 (IL-1)] after endotoxin challenge. These findings suggest that the 
      increased resistance to endotoxin in vivo after stress protein induction could be 
      explained by an altered pattern of inflammatory mediator release. Therefore, we 
      measured the time course of thromboxane-B2 (TxB2), 6-keto-PGF1 alpha, platelet 
      activating factor (PAF), TNF alpha, interleukin-1 beta (IL-1 beta), and 
      interleukin-6 (IL-6) formation with and without induction of the stress response 
      in an established porcine model of recurrent endotoxemia (Klosterhalfen et al., 
      Biochem Pharmacol 43: 2103-2109, 1992). Induction of the stress response was done 
      by a pretreatment with Zn2+ (25 mg/kg zinc-bis-(DL-hydrogenasparate = 5 mg/kg 
      Zn2+). Pretreatment with Zn2+ prior to lipopolysaccharide (LPS) infusion induced 
      an increased heat shock protein 70 and metallothionein expression in the lungs, 
      liver, and kidneys and increased plasma levels of TNF alpha, IL-1 beta, IL-6, and 
      TxB2 as opposed to untreated controls. After LPS infusion, however, pretreated 
      animals showed significantly decreased peak plasma levels of all mediators as 
      opposed to the untreated group. The time course of mediator release was identical 
      with the decreasing and increasing three peak profiles described previously. 
      Hemodynamic data presented significantly decreased peak pulmonary artery 
      pressures and significantly altered hypodynamic/hyperdynamic cardiac output 
      levels in the pretreated group. In conclusion, the data show that the induction 
      of stress proteins by Zn2+ could be a practicable strategy to prevent sepsis.
FAU - Klosterhalfen, B
AU  - Klosterhalfen B
AD  - Department of Surgery, Technical University of Aachen, Germany.
FAU - Tons, C
AU  - Tons C
FAU - Hauptmann, S
AU  - Hauptmann S
FAU - Tietze, L
AU  - Tietze L
FAU - Offner, F A
AU  - Offner FA
FAU - Kupper, W
AU  - Kupper W
FAU - Kirkpatrick, C J
AU  - Kirkpatrick CJ
LA  - eng
PT  - Journal Article
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (HSP70 Heat-Shock Proteins)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-6)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Platelet Activating Factor)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 30KYC7MIAI (Aspartic Acid)
RN  - 54397-85-2 (Thromboxane B2)
RN  - 58962-34-8 (6-Ketoprostaglandin F1 alpha)
RN  - 9038-94-2 (Metallothionein)
RN  - J41CSQ7QDS (Zinc)
SB  - IM
MH  - 6-Ketoprostaglandin F1 alpha/biosynthesis
MH  - Animals
MH  - Aspartic Acid/pharmacology
MH  - Blood Pressure/drug effects
MH  - Cardiac Output/drug effects
MH  - Disease Models, Animal
MH  - Endotoxemia/genetics/*physiopathology/*prevention & control
MH  - Gene Expression/drug effects
MH  - HSP70 Heat-Shock Proteins/*biosynthesis/genetics
MH  - Inflammation Mediators/*physiology
MH  - Interleukin-1/biosynthesis
MH  - Interleukin-6/biosynthesis
MH  - Kidney/drug effects/metabolism
MH  - Lipopolysaccharides/toxicity
MH  - Metallothionein/*biosynthesis/genetics
MH  - Platelet Activating Factor/biosynthesis
MH  - Pulmonary Artery/drug effects
MH  - Recurrence
MH  - Swine
MH  - Thromboxane B2/biosynthesis
MH  - Tumor Necrosis Factor-alpha/biosynthesis
MH  - Zinc/*pharmacology
EDAT- 1996/10/25 00:00
MHDA- 1996/10/25 00:01
CRDT- 1996/10/25 00:00
PHST- 1996/10/25 00:00 [pubmed]
PHST- 1996/10/25 00:01 [medline]
PHST- 1996/10/25 00:00 [entrez]
AID - 0006-2952(96)00469-8 [pii]
AID - 10.1016/0006-2952(96)00469-8 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 1996 Oct 25;52(8):1201-10. doi: 10.1016/0006-2952(96)00469-8.