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PubMed1981

Rat blood leucocytes, unlike rabbit leucocytes, do not generate procoagulant activity on exposure to endotoxin.

We have investigated the ability of rat and rabbit leucocytes to generate procoagulant activity (PCA) in response to endotoxin in vitro and in vivo. On prolonged incubation with endotoxin (10 micrograms/ml f.c.) isolated rabbit leucocytes developed strong PCA as measured by clotting and amidolytic assay. In contrast, rat leucocytes failed to produce any PCA even in the presence of huge amounts of endotoxin (200 micrograms/mol f.c.). When rabbits were given two spaced endotoxin injections (25 micrograms/kg consistently showed marked PCA. Again, unlike in the rabbit, rat leucocytes obtained after 2 endotoxin injections (up to 2 mg/kg body wt) showed absolutely no PCA. These findings support the view that leucocytes are involved in endotoxin-induced disseminated intravascular coagulation (DIC) in rabbits. On the other hand the poor response of rat leucocytes to endotoxin might help explain the resistance of rats to DIC and Sanarelli-Shwartzman reaction.

Animals↗
PubMed1995

Metabolism of cysteinyl leukotrienes in the perfused rat liver: the influence of endotoxin pretreatment and the cellular hydration state.

The influence of endotoxin on the hepatic metabolism and elimination of 3H-leukotriene C4 (LTC4) and 3H-leukotriene E4 was studied in the single-pass perfused rat liver. Endotoxin (4 mg/kg body mass) was injected intraperitoneally 8 to 10 hours before livers were isolated for perfusion. Tritiated leukotriene C4 and leukotriene E4 (10 nmol/L) were infused for 5 minutes, and metabolites in bile were determined by high-pressure liquid chromatography. In livers without endotoxin pretreatment, single-pass uptake of LTC4 was 77.3% +/- 3.2%, and 73.8% +/- 1.8% of the radioactivity taken up was excreted into the bile within 80 minutes. In endotoxin-pretreated livers, LTC4 uptake was 62.8% +/- 3.5% and only 31.2% +/- 1.5% of the radioactivity taken up was eliminated into the bile within 80 minutes. Bile flow was reduced to 0.20 +/- 0.07 microL/min, compared with 1.18 +/- 0.18 microL/g/min in untreated livers. Biliary excretion of infused 3H-LTE4 was also reduced in endotoxin-pretreated livers (31.5% +/- 6.1% compared with 61.4% +/- 3.3% without endotoxin pretreatment), whereas uptake was not significantly different. The effect of cellular hydration state on leukotriene processing was also investigated. Anisoosmotic cell volume changes did not influence uptake and biliary excretion of 3H-LTC4 and its metabolism in control livers. In endotoxin-pretreated livers, however, cell swelling induced by hypotonic perfusion media (225 mOsm/L) or by 3 mmol/L glutamine increased biliary elimination of the radioactivity taken up by 68% and 54%, respectively. Bile flow was also stimulated (0.31 +/- 0.09 microL/g/min and 0.46 +/- 0.01 microL/g/min, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Antiproteases modulate bronchial epithelial cell responses to endotoxin.

Escherichia coli endotoxin (0.1 to 1000 micrograms/ml) stimulated the release of neutrophil chemotactic activity (P < 0.001) and induced bronchial epithelial cell (BEC) cytotoxicity assessed by lactate dehydrogenase release (P < 0.001). Endotoxin (100 micrograms/ml) inhibited BEC accumulation (P < 0.001). In the present study, we investigated the role of proteolytic activity of BECs per se in response to endotoxin. Several structurally and functionally different antiproteases, alpha 1 protease inhibitor, soybean trypsin inhibitor, two chloromethyl ketone derivatives (N-tosyl-L-lysine chloromethyl ketone and methoxysuccinyl-Ala-Ala-Pro-Val chloromethyl ketone), and L-658,758, a neutrophil elastase inhibitor, attenuated the release of neutrophil chemotactic activity and lactate dehydrogenase (P < 0.01). alpha 1-Protease inhibitor and N-tosyl-L-lysine chloromethyl ketone attenuated the inhibition of BEC accumulation by endotoxin (P < 0.001). The proteolytic enzyme activity measured by synthetic substrates revealed that endotoxin significantly augmented the serine proteolytic activity in the cell layers. Culture supernatant fluids and cell lysates of BECs in the presence of endotoxin solubilized 14C-labeled casein. These data suggest that responses of BECs to endotoxin may involve activation of cellular proteolytic activity.

Bronchi↗
PubMed1976

Effect of endotoxin and trypsin on the blood pressor response to catecholamines in normo- and hypothermic rabbits.

The action of endotoxin, trypsin or hypothermia on the vascular reactivity to catecholamines was investigated in rabbits, and with trypsin in normothermic dogs as well. In rabbits, LD10 of Escherichia coli 0111 endotoxin increased the blood pressor effect of i.v. adrenaline or noradrenaline with maxima at 60-90 min. LD50 endotoxin elicited a vascular hyporeactivity to catecholamines within an hour. 22 hours later, however, a hyperreactivity to catecholamines developed. At this time, repeated administration of LD50 endotoxin did not reduce the increased catecholamine responsiveness. Trypsin (i.v. 1.5 mg/kg) also potentiated the pressor effect of catecholamines in rabbits and dogs with maxima at 5-10 min. Higher trypsin doses induced a hyporeactivity. LD50 endotoxin in a single or a repeated dose after 22 hours did not decrease the blood pressure of cooled rabbits and failed to alter the vascular reactivity to adrenaline or noradrenaline. The blood pressure effect of trypsin differed in character in normo- and hypothermic rabbits, depending on the depth of cooling. Low body temperature eliminated the potentiating effect of trypsin to the blood pressor action of catecholamines. In normothermic rabbits pretreated with amino-pyrine and phenylbutazone, the blood pressure and the catecholamine potentiation effects of endotoxin or trypsin were inhibited or considerably reduced. The results support the significance of altered vascular reactivity to catecholamines under different pathologic conditions where endotoxin and/or proteases may occur.

Aminopyrine↗
PubMed1976

Detection of bacterial endotoxin in antitumor agents.

The Limulus amebocyte lysate assay was used to detect the presence of bacterial endotoxin in a variety of chemotherapeutic agents currently in use. Results were quantitated using a standard Escherichia coli endotoxin curve. Relative concentrations of endotoxin ranging from 0.1 to 63 ng/ml were detected in individual lots of L-asparaginase, 5-azacytidine, bleomycin, DTIC, actinomycin D, adriamycin, and vinblastine diluted to normal concentrations for injection. When multiple lots of a given drug were tested, at least one lot produced a negative assay, indicating less than 0.1 ng/ml of endotoxin in 50% of these drugs. All lots of cytosine arabinoside, cyclophosphamide, daunorubicin, vincristine, and streptozotocin tested had less than 0.1 ng/ml of endotoxin. Inactivation kinetics of the Limulus-positive drug material in dilute alkali solutions were identical to those of E. coli endotoxin. The Limulus lysate test is a rapid and specific method for the detection of small amounts of bacterial endotoxin contaminating parenteral preparations of antitumor agents.

Animals↗
PubMed1994

Priming of phagocytes for reactive oxygen production during hepatic ischemia-reperfusion potentiates the susceptibility for endotoxin-induced liver injury.

Plasma levels of glutathione disulfide (GSSG) as an indicator of a vascular oxidant stress, tumor necrosis factor-alpha (TNF-alpha) formation, and liver injury (alanine aminotransferase activity, histology) were monitored in male Fischer rats after 30 min of hepatic ischemia followed by up to 4 hr of reperfusion. The injection of 1 mg/kg Salmonella enteritidis endotoxin at 30 min of reflow potentiated the postischemic oxidant stress and liver injury. TNF-alpha levels increased from 10 +/- 7 pg/ml (baseline) to 3,553 +/- 738 pg/ml after ischemia-reperfusion followed by endotoxin, or to 3,670 +/- 508 pg/ml after endotoxin alone. Depletion of serum complement before ischemia attenuated the endotoxin-mediated increase of reactive oxygen formation by 70% but did not affect TNF-alpha levels. Complement activation with cobra venom factor (CVF) during reperfusion had an effect similar to that of endotoxin on the oxidant stress and liver injury. CVF did not increase TNF-alpha formation during reperfusion. Kupffer cells and neutrophils isolated from the postischemic liver 2.5 hr after endotoxin injection generated 600% and 400% more superoxide, respectively, than cells isolated from control livers. The results demonstrate a substantial priming of hepatic phagocytes for reactive oxygen production but not TNF-alpha formation, even after short periods of hepatic ischemia, and the vulnerability of the postischemic liver to severe endotoxin-induced injury. Activated complement seems to be mainly responsible for the effects. These results may explain the high risk for hepatic failure after extensive liver resection and hypovolemic shock.

Adenosine Triphosphate↗
PubMed1994

Neutralization of IL-8 inhibits neutrophil influx in a rabbit model of endotoxin-induced pleurisy.

Although the potent neutrophil chemotaxin, IL-8, is a known product of endotoxin-stimulated cells in vitro, the contribution of IL-8 to neutrophil recruitment in Gram-negative endotoxin inflammation in vivo is unknown. To determine whether neutralization of IL-8 would decrease endotoxin-induced neutrophil influx, we generated neutralizing mAbs to rabbit rIL-8 for use in our rabbit model of endotoxin-induced pleurisy. One mAb, ARIL8.2, specifically inhibited both rabbit rIL-8-induced chemotactic activity and activation of the rabbit IL-8 receptor transfected in 293 cells. Anesthetized rabbits with in-dwelling pleural catheters received either neutralizing mAb (ARIL8.2; 1 mg/kg) or irrelevant isotype-matched mAb (anti-HIV gp120) i.v. 1 h before as well as intrapleurally (20 micrograms/ml) at the time of intrapleural instillation of Escherichia coli endotoxin (200 ng bilaterally). ARIL8.2 blocked 77% of endotoxin-induced neutrophil influx (21 +/- 2 (SE) x 10(6) (ARIL8.2) vs 91 +/- 15 x 10(6) (anti-gp120) (p < 0.0001)). By Western analysis, a band corresponding to rabbit IL-8 was detected in the pleural liquid of rabbits in both groups. By ELISA, however, the concentration of free, unbound IL-8 in the pleural liquid was significantly less in the ARIL8.2 group than in the anti-gp120 group for at least 4 h, confirming that ARIL8.2 bound the IL-8 generated in vivo during that time. We conclude that neutralization of IL-8 profoundly inhibits neutrophil recruitment in endotoxin-induced pleurisy indicating that IL-8 is a major chemotactic factor in this model of acute inflammation.

Animals↗
PubMed1993

Endotoxin as a therapeutic target in septic shock.

Endotoxin initiates a broad inflammatory response in mammals that has many similarities to de novo septic shock in patients. The presumed role of endotoxin in septic shock has led to the investigation of antiendotoxin therapies for the treatment of this syndrome. However, a causative role for endotoxin in human septic shock has not been established. Recent information about the biochemistry of endotoxin, mechanisms of endotoxin-induced cell activation, and the pathogenesis of septic shock has provided insights useful to the development of new antiendotoxin agents, but also has raised concerns about the suitability of endotoxin as a therapeutic target. Definitive proof of the pathogenic importance of endotoxin in human septic shock will depend upon demonstrating that a putative antiendotoxin therapy has clinical efficacy.

Animals↗
PubMed1993

The effect of two-domain tissue factor pathway inhibitor on endotoxin-induced disseminated intravascular coagulation in rabbits.

Disseminated intravascular coagulation (DIC) is a common complication in sepsis, and may result from endotoxin-induced exposure of tissue factor on the surface of monocytes and endothelial cells. Tissue factor pathway inhibitor (TFPI) is a factor Xa-dependent feedback inhibitor of the tissue factor-factor VIIa complex. In the present study the effect on DIC of a two-domain TFPI analogue (2D-TFPI), consisting of the first two Kunitz domains of TFPI but lacking the third domain, was tested. DIC was induced in rabbits by two intravenous bolus injections of endotoxin from Escherichia coli (10 and 50 micrograms/kg) 24 h apart. Simultaneously with the last endotoxin injection an infusion of 2D-TFPI (0, 0.3, 1.0 or 3.0 mg/kg/h) was given. Blood samples were obtained at 0 h, 24 h and 31 h. At 31 h the animals were sacrificed and the kidneys were submitted to histological examination. The degree of fibrin deposition in glomeruli was scored blindly using an arbitrary scale from 0 to 3. Between 24 and 31 h the group receiving endotoxin alone showed a significant decrease in platelet count (65%), plasma fibrinogen (41%), antithrombin III (25%), and factor VIII (63%), and a significant prolongation of the aPTT (14%). Furthermore, massive fibrin deposition was detected in the renal glomeruli at 31 h. Infusions of 2D-TFPI inhibited all the endotoxin-induced changes in a dose-dependent manner. In conclusion, the data demonstrate that inhibition of the TF/FVIIa complex by infusion of 2D-TFPI significantly counteracts endotoxin-induced coagulopathy in rabbits, and might thus be an attractive drug for treatment of endotoxin-induced DIC in humans.

Animals↗
PubMed1993

[Bacterial endotoxins: relationship between chemical structure and biological effect].

Gram-negative bacteria carry on their surface endotoxins, which are essential for bacterial growth and survival. If released from the bacterial cell, endotoxins induce in higher organisms a great variety of pathophysiological effects. Chemically, endotoxins constitute lipopolysaccharides (LPS), the lipid component (termed lipid A) of which is responsible for the induction of endotoxin effects. The structural and conformational parameters, endowing lipid A with its potent bioactivity, have been well characterized. The toxic effects of endotoxins are initiated by the specific interaction of lipid A with macrophages/monocytes resulting in the production of peptide or lipid mediators. This interaction is governed by a unique (toxic) conformation of lipid A on the one hand, and by specific cellular receptors on the other. The interaction and subsequent mediator production can be specifically and antagonistically inhibited by lipid A partial structures. A recently developed monoclonal anti-LPS-antibody cross-reacts with endotoxins of various bacterial origin, and it cross-protects against harmful endotoxin effects such as pyrogenicity and lethality.

Animals↗
PubMed1993

Age-related differences in responses to endotoxin infusion in unanesthetized piglets.

Newborn endotoxic shock syndrome is associated with high morbidity and mortality, yet presents with different clinical manifestations than in older patients. To determine the influence of age on hemodynamic and metabolic responses to endotoxin, we developed a chronically instrumented endotoxic shock model using eight 1-3-day-old and seven 2-3-week-old piglets. Three days after surgery, 10 mg/kg of endotoxin was infused intravenously over 10 min in the younger group, and 5-10 mg/kg was given to the older animals. Two older piglets died immediately after infusion of 5 mg/kg of endotoxin, and five of the seven died within 4 hr, while all eight younger animals lived longer than 4 hr. Pulmonary artery pressure increased significantly after endotoxin in both groups, and there were no differences between groups. Systemic artery pressure and cardiac index fell by 44 +/- 10% and 70 +/- 15%, respectively, 5 min after endotoxin infusion in the older group, while these values did not change significantly in the younger group. Endotoxin infusion also caused greater elevation in pulmonary vascular resistance index in the older animals. In the later phase, which began 30 min after endotoxin, both groups displayed systemic hypotension and pulmonary hypertension, and the groups did not differ from one another in this regard. With progression of endotoxic shock, more severe metabolic acidosis developed in the older animals than in the younger animals. Plasma thromboxane B2 levels in the older group were about double those in younger piglets. Plasma 6-keto-PGF1 alpha and TNF alpha levels in both groups were similar and were significantly increased in the later phase.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Comparison of the induction of endotoxin tolerance in endotoxemia and peritonitis by monophosphoryl lipid A and lipopolysaccharide.

We compared the induction of endotoxin tolerance with Salmonella minnesota monophosphoryl lipid A (MPL), a nontoxic derivative of lipid A, and S. minnesota endotoxin (LPS) in lethal endotoxemia and peritonitis. Lethal endotoxemia was induced by injecting 750 micrograms/mouse LPS intravenously. Cecal ligation and perforation was used to induce peritonitis. Tumor necrosis factor (TNF) was measured by immunoassay at 2 hr after lethal endotoxin infusion and 24 hr after peritonitis. A dose of 0.1 micrograms/mouse of MPL or LPS significantly reduced endotoxin mortality from 100% to 50% and 27%, respectively (P < 0.05). The LD50 for a 0.1 micrograms dose of MPL was 750 micrograms of LPS and the LD50 for a 0.1 micrograms dose of LPS was 1150 micrograms of endotoxin (P < 0.05). TNF levels decreased linearly when increasing doses of MPL and LPS were used to induce tolerance. At higher pretreatment doses of LPS, survival benefits were attenuated despite the reduction in TNF levels. A 25 micrograms dose of LPS reduced mortality from peritonitis from 93% to 45% (P < 0.05). Although MPL reduced short-term mortality, overall mortality was not significantly reduced despite using large doses of MPL. TNF levels peaked at 24 hr and were significantly lower than those following lethal endotoxemia. The induction of endotoxin tolerance by LPS and MPL is dose dependent, and LPS is modestly more effective in inducing endotoxin tolerance than MPL. Both LPS and MPL are significantly less effective in protecting against lethality from peritonitis.

Animals↗
PubMed1993

Hemodynamic responses to changes in carotid sinus pressure after endotoxin and ibuprofen.

The hemodynamic responses to changes in carotid sinus pressure (CSP) were evaluated in nine pentobarbital-anesthetized dogs during control, endotoxin-treatment, and ibuprofen (after endotoxin) treatment periods. Both carotid sinuses were isolated and perfused at varying pressures with oxygenated blood in the vagotomized animal. Alterations in carotid sinus pressure and the resultant responses were measured at 15-min intervals during a 30-min control period, for 60 min after 1 mg/kg endotoxin, and for 60 min after 10 mg/kg ibuprofen given after endotoxin. The results showed a reduction in calculated gain for mean arterial pressure (MAP) (change in arterial pressure/change in CSP), heart rate, and peripheral resistance (TPR) after endotoxin, without a corresponding reduction in cardiac output (CO) gain. These gain changes were accompanied by a decrease in absolute MAP, CO, and TPR. An indicator for cardiac performance gain also increased. Relatively, arterial pressure was partially maintained by an increase in CO despite a loss in ability to vasoconstrict. Ibuprofen failed to correct the MAP gain, and only partially restored MAP, but shifted a greater relative response to peripheral resistance. To test if TPR would also decrease if the decrease in CO was prevented, three additional animals were studied with a pump in series with the heart to maintain CO; TPR again dropped after endotoxin. The results indicate a loss of peripheral arterial tone after endotoxin, partially restored by ibuprofen. The CO response indicates a peripheral vascular failure rather than a central or carotid sinus failure mechanism.

Animals↗
PubMed1995

Short-time rabbit model of endotoxin-induced hypercoagulability.

We describe a short-time endotoxin-induced rabbit model of hypercoagulability for the study of the coagulation cascade and the therapeutic effects of coagulation inhibitors. Cardiorespiratory function was maintained in rabbits under general anesthesia and standardized mechanical ventilation (tidal volume, 6 ml/kg; 60 breaths/min) via tracheostomy and low-dose inotropic support. Coagulation parameters such as prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen concentration, platelet count, fibrin monomers, D-dimers, antithrombin III and factor XIII activities, thrombelastography, and platelet aggregometry were measured during a 4-h period after sequential double endotoxin administration (80 and 40 micrograms/kg of body weight, intravenously). Mean arterial pressure and arterial and central venous blood gas tensions were monitored. Global clotting, activation parameters of coagulation, and leukocyte count deteriorated significantly in the endotoxin-treated animals but was mainly unaltered in controls (P < 0.05). Tissue specimens of the lungs, liver, brain, and kidneys were examined. Endotoxin-induced, disseminated fibrin deposition was found in the lungs and liver (P < 0.01). We conclude that this short-time model of hypercoagulability in rabbits reliably induced disseminated intravascular coagulation. Tracheostomy and mechanical ventilation provided a reproducible model in which the differences between the controls and the endotoxin-treated animals were exclusively due to administration of endotoxin and not to unforeseen complications of the respiratory system. This model allows the study of therapeutic effects of coagulation inhibitors on endotoxin-induced changes.

Animals↗
PubMed1996

Effect of oral administration of flunixin meglumine on the inflammatory response to endotoxin in heifers.

OBJECTIVE: To compare the effect of oral and IV administrations of flunixin meglumine on the endotoxin-induced inflammatory response in heifers. DESIGN: The study was conducted in 2 experimental sets in which heifers were exposed to low IV doses of Escherichia coli endotoxin. Within each set, heifers were allocated to 3 treatment groups; pretreatment with flunixin meglumine orally and IV prior to endotoxin administration, or endotoxin administration only. The dose of flunixin used was the recommended therapeutic dose in cattle. ANIMALS: 11 clinically normal heifers weighing from 400 to 640 kg. PROCEDURE: A permanent cannula was inserted into the jugular vein on the day prior to the experiment. Blood samples were collected regularly during the experiment and analyzed for the content of prostaglandin F2 alpha metabolite, cortisol, blood mononuclear cells, and polymorphonuclear neutrophilic leukocytes and rectal temperature was measured. RESULTS: Endotoxin administration caused clinical signs and hematologic changes characteristic of endotoxemia in cattle. Flunixin administered orally prior to experimentally induced endotoxemia exerted an effect equal to that after its IV administration. Significant increases in rectal temperature and prostaglandin F2 alpha metabolite concentrations after administration of endotoxin were abrogated when the heifers were pretreated with flunixin, irrespective of route of administration. Cortisol concentrations were lower after pretreatment with flunixin. However, flunixin did not prevent the decrease in blood mononuclear cells and polymorphonuclear neutrophilic leukocytes seen after endotoxin administration. CONCLUSION: Owing to no major difference in the inflammatory response between oral and IV flunixin dosing, flunixin granules may be an alternative to parenteral use in bovine practice.

Administration, Oral↗
PubMed1997

Endotoxin concentration in contact lens storage cases.

BACKGROUND: The contamination of contact lens storage cases by gram-negative bacteria has been associated with ulcerative keratitis. This study investigated the concentration of endotoxin, a substance produced by gram-negative bacteria, in contact lens cases. METHODS: The limulus amebocyte lysate (LAL) test was used to measure the concentration of endotoxin in the storage cases of 27 contact lens wearers. The units of concentration used were endotoxin units per ml (EU/ml). The type of storage solution used by each patient, as well as other aspects of lens care and use, were recorded. RESULTS: Twenty-one storage cases--78% of those tested--contained measurable amounts of toxin. Two cases contained extremely high concentrations of endotoxin: 60 EU/ml and 300 EU/ml. Both cases were from persons using Opti-Free. Cases from six persons using Opti-Free accounted for five of the top seven endotoxin concentrations when cases were ranked on that basis. Fewer hours of daily lens wear and lower lens age were also possibly associated with higher concentrations of endotoxin, although those associations may have resulted by chance (p = 0.057 and p = 0.095, respectively). CONCLUSIONS: The LAL test was useful in estimating the degree of contamination of cases by gram-negative bacteria. Most cases contained measurable amounts of endotoxin, indicating at least some contamination by gram-negative bacteria. The effectivity of Opti-Free in inhibition of bacterial growth in contact lens cases should be investigated further.

Biofilms↗
PubMed1997

Concentrations of bile and serum endotoxin and serum cytokines after biliary drainage for acute cholangitis.

Endotoxin contributes to cholangitis. We measured concentrations of bile and serum endotoxin and serum cytokines after biliary drainage for obstructive jaundice with or without acute cholangitis. Patients who underwent percutaneous transhepatic cholangiodrainage (PTCD) in 1995 were classified as having acute cholangitis (group A; n = 11), having a history of acute cholangitis (group B; n = 5), or not having a history of acute cholangitis (group C; n = 13). Bile endotoxin was positive (above the cut-off value) in all patients in groups A and B, and in five patients in group C. The mean concentration of bile endotoxin was significantly higher in groups A and B than in group C. After PTCD, the bile endotoxin level decreased more slowly in group A than in the other groups. Before PTCD, the mean serum levels of IL-1 receptor antagonist (IL-1ra), IL-6, and IL-8 were higher in group A than the other groups. The serum levels of IL-1ra and IL-6 before PTCD were significantly higher when the acute cholangitis was more severe. The mean serum levels of cytokines increased just after PTCD and then decreased. In group A, the serum level of IL-6 at 5 h after PTCD was significantly correlated to the endotoxin level in bile at this time. Increases in cytokines may participate in the pathophysiological changes of acute cholangitis. Biliary drainage for acute cholangitis causes improvement by decreasing the bile endotoxin level addition to decreasing bile-duct pressure, thereby preventing excess production of inflammatory cytokines.

Acute Disease↗
PubMed1976

The effect of leukocyte and platelet transfusion on the activation of intravascular coagulation by endotoxin in granulocytopenic and thrombocytopenic rabbits.

The effect of transfusion of peritoneal leukocytes, platelets, or cell suspension medium on the activation of intravascular coagulation and on the generation of capillary microclots was studied in 51 granulocytopenic and thrombocytopenic rabbits. Granulocytopenia and thrombocytopenia induced by feeding the cytoxic drug busulfan prevented the activation of intravascular coagulation and the occurrence of renal glomerular microclots after two injections of endotoxin. The transfusion of platelets into busulfan-pretreated rabbits increased the mean platelet count from 2,400 to 205,000 cells/mul, but platelet-transfused rabbits did not exhibit activation of intravascular coagulation after endotoxin injection. If however, granulocytopenic and thrombocytopenic rabbits were transfused with peritoneal leukocytes (1.0 X 10(9) cells/kg) before the second injection of endotoxin, activation of intravascular coagulation occurred, and microclot formation in renal glomerular capillaries was observed in a high percentage of animals. Positive reactions to endotoxin were obtained in leukocyte-transfused rabbits even with platelet counts of 1,000 cells/mul before the second injection of endotoxin. Thus platelets do not seem to be essentially involved in the activation of intravascular coagulation by endotoxin, whereas the presence of leukocytes is required for triggering endotoxin-induced generalized intravascular coagulation.

Agranulocytosis↗