Pretreatment with Ibuprofen Augments Circulating Tumor Necrosis Factor- , Interleukin-6, and Elastase during Acute Endotoxinemia

Spinas, Giatgen A.; Bloesch, D.; Keller, Ulrich; Zimmerli, Werner; Cammisuli, Salvatore

doi:10.1093/infdis/163.1.89

Cited by 128 publications

(63 citation statements)

References 35 publications

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“…These eicosanoids are considered to be primarily proinflammatory. The means and standard errors for prostanoid production by decidual explants in the first 24 h of culture taken from mice killed 3 h after injection with 10 Mug of LPS or vehicle are shown in Fig. 4.…”

Section: Methodsmentioning

confidence: 99%

“…Fig. 5 shows a representative Western blot prepared using decidual microsomal proteins taken from animals that were killed at serial time points after injection with 10 Mig of LPS or vehicle and detected with an antibody against COX-2. COX-2 was present at low levels in decidua from untreated and PBStreated mice.…”

Section: Methodsmentioning

confidence: 99%

“…LPS induces a marked inflammatory response that is mediated primarily by the activation of macrophages and the release of cytokines and prostanoids (8). The inhibition of prostanoid production with cyclooxygenase (COX)' inhibitors attenuates many of the clinical manifestations of bacterial infection (9,10).…”

Section: Introductionmentioning

confidence: 99%

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Bacterial lipopolysaccharide-mediated fetal death. Production of a newly recognized form of inducible cyclooxygenase (COX-2) in murine decidua in response to lipopolysaccharide.

et al. 1995

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Maternal infection is a cause of spontaneous abortion and preterm labor in humans, but the pathophysiology is unclear. We hypothesized that eicosanoids play an important role in infection-driven pregnancy loss. To investigate this hypothesis, we administered lipopolysaccharide (LPS) to pregnant C3H/HeN mice and found that LPS administration caused fetal death in a dose-dependent fashion. Pretreatment with indomethacin significantly decreased the proportion of fetal death from 83% to < 25% in mice injected with 10 jag of LPS. Also, decidual explants from LPStreated mice produced significantly more inflammatory eicosanoids, including prostaglandins E2 and F2. and thromboxane B2, than controls. We investigated the regulatory mechanisms responsible for increased decidual prostanoid production in response to LPS. Western and Northern blots demonstrated that decidual protein and mRNA levels of a recently recognized highly inducible form of cyclooxygenase, COX-2, were substantially increased in mice treated with LPS. Induction of COX-2 was rapid: mRNA was detected 30 min after LPS injection. In contrast, another form of cyclooxygenase, COX-1, was only minimally induced in response to LPS. Our data indicate that LPS induces decidual prostanoid production via increased COX-2 expression. Since LPS-mediated fetal death is markedly diminished by pretreatment with indomethacin, COX-2-mediated eicosanoid production is likely a key pathophysiologic event in LPS-mediated fetal death. (J. Clin. Invest. 1995. 95:725-731.)

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Bacterial lipopolysaccharide-mediated fetal death. Production of a newly recognized form of inducible cyclooxygenase (COX-2) in murine decidua in response to lipopolysaccharide.

et al. 1995

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“…Recently we and other investigators have reported the induction of significant levels of circulating TNF by experimental administration ofEscherichia coli endotoxin to healthy volunteers (13)(14)(15). Pretreatment of the volunteers with ibuprofen, an inhibitor of prostaglandin synthesis, greatly enhanced circulating TNF concentrations (14,15) while blunting the clinical response to endotoxin.…”

Section: Introductionmentioning

confidence: 91%

Release of soluble receptors for tumor necrosis factor (TNF) in relation to circulating TNF during experimental endotoxinemia.

Spinas

Keller²,

Brockhaus³

1992

J. Clin. Invest.

225

103

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Serial plasma samples from human volunteers obtained after intravenous administration of Escherichia coli endotoxin were analyzed for the presence of circulating soluble tumor necrosis factor receptors (sTNFR). A four-to fivefold increase of type A (p75) and type B (p55) sTNFR was observed 3 h after endotoxin challenge. Pretreatment of the volunteers with ibuprofen before the injection of endotoxin resulted in a slight increase (3.87±0.2 vs. 3.27±03 ng/ml) and temporal shift of sTNFR-A release concurrent to a marked augmentation of TNF levels (603±118 vs. 338±56 pg/nml) as compared to the group without ibuprofen pretreatment. There was a significant correlation between peak sTNFR-A levels and peak TNF levels in the individual probands (r = 0.52, P = 0.04). On the contrary, release kinetics and plasma concentrations of sTNFR-B were identical in both groups (738±0.69 vs. 7.44±033 ng/ml) and no correlation with individual TNF levels was observed. The amount of sTNFR liberated upon endotoxin challenge was not sufficient to block TNF-mediated cytotoxic effects. Our data indicate that the release in vivo of type A and type B sTNFR upon a short exposure to endotoxin is regulated differently. (J. Clin. Invest. 1992. 90:533-536.)

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“…The serum concentration of sCD 14 is ,...., I millionfold higher than that ofcytokines [8]. Although much is known about cytokine liberation during experimental endotoxemia or sepsis, little is known about sCD 14 in these conditions [9][10][11][12]. Because CD 14 is the principle LPS receptor, the serum concentration ofsCD 14 may be modified during endotoxemia or sepsis.…”

mentioning

confidence: 99%

Increased Circulating Soluble Cd14 Is Associated With High Mortality In Gram-Negative Septic Shock

Landmann

Zimmerli²,

Sansano³

et al. 1995

Journal of Infectious Diseases

Self Cite

193

124

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The soluble glycoprotein sCD 14 binds lipopolysaccharide, a complex that activates endothelial cells and that may be crucial in gram-negative sepsis, Therefore, serum sCD14 was analyzed in 54 patients with gram-negative septic shock and in 26 healthy controls, sCD14 was tested by ELISA and Western blotting, Patients had higher sCD14 concentrations than controls (median, 3.23 vs. 2.48 #!g/mL, P = .002). Increased levels were associated with high mortality (median, 4.2 #Lg/mL in nonsurvivors vs. 2.8 #!g/mL in survivors, P = .001). sCD14 was found in two isoforms (49 and 55 kDa) in monocyte cultures. In sera only one of either form was detectable. Controls had the 49-kDa form, and patients had either the 49-or 55-kDa form, but patients with high levels of sCD14 had only the 55-kDa form. Twenty-one (53%) of 39 with the 55-kDa form and 8 (57%) of 14 with the 49-kDa form died. Thus, the level of sCD14 but not its biochemical form had a prognostic value in patients with gram-negative septic shock.Lipopolysaccharide (LPS) plays a key role in the pathophysiology of sepsis [I]. The LPS receptor on myeloid cells is the phosphatidylinositol-Iinked membrane glycoprotein CD 14 [2]. CD 14 occurs in a membrane-associated form and as a soluble (s) molecule [3,4]. sCD 14 is derived from the monocytic cell line Mono-Mac 6 in two forms [5]: A 48-kDa form is shed from the membrane of monocytes and MonoMac 6 cells [6,7], and a 56-kDa form is detectable in metabolically labeled Mono-Mac 6 cells and in sCD 14 purified from urine [3,5]. The serum concentration of sCD 14 is ,...., I millionfold higher than that ofcytokines [8]. Although much is known about cytokine liberation during experimental endotoxemia or sepsis, little is known about sCD 14 in these conditions [9][10][11][12]. Because CD 14 is the principle LPS receptor, the serum concentration ofsCD 14 may be modified during endotoxemia or sepsis. The physiologic role of sCD 14 is unknown. It could act as a scavenger by neutralizing circulating LPS [13] shown that complexes ofsCD 14 with LPS activate these cells [14,15].We measured sequential serum concentrations of sCD 14 in 54 patients with gram-negative septic shock, compared these with levels in normal controls, and correlated sCD 14 levels with patient outcome. We also determined the biochemical form of serum sCD 14 by Western blotting and compared it with sCD 14 derived from normal monocytes. MethodsPatients. The study population comprised 54 patients (33 males, 21 females) with documented gram-negative septic shock. Their median age was 58 years (range, 7-78). All were part of a previously described study that compared the efficacy of J5 hyperimmunoglobulin (n = 22) with standard intravenously (iv) administered IgG (n = 32) (Sandoglobulin; Sandoz Pharmaceuticals, Basel, Switzerland) [16]. The etiology ofseptic shock was established by the isolation of gram-negative bacteria from blood in 37 patients (69%). Of these, 30 had monomicrobial and 7 had polymicrobial bacteremia. Seventeen patients (3 t %) had documented gram-nega...

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Pretreatment with Ibuprofen Augments Circulating Tumor Necrosis Factor- , Interleukin-6, and Elastase during Acute Endotoxinemia

Cited by 128 publications

References 35 publications

Bacterial lipopolysaccharide-mediated fetal death. Production of a newly recognized form of inducible cyclooxygenase (COX-2) in murine decidua in response to lipopolysaccharide.

Bacterial lipopolysaccharide-mediated fetal death. Production of a newly recognized form of inducible cyclooxygenase (COX-2) in murine decidua in response to lipopolysaccharide.

Release of soluble receptors for tumor necrosis factor (TNF) in relation to circulating TNF during experimental endotoxinemia.

Increased Circulating Soluble Cd14 Is Associated With High Mortality In Gram-Negative Septic Shock

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