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At least 217 records · Page 12Linked to original sources
PubMed2006

Endotoxin adsorption therapy for septic shock using polymyxin B-immobilized fibers (PMX): evaluation by high-sensitivity endotoxin assay and measurement of the cytokine production capacity.

Because of its low sensitivity, the conventional measurement method for endotoxin (ET) is not the most appropriate for monitoring the effect of ET adsorption therapy. Thus, the efficacy of ET adsorption therapy was investigated using a newly developed high-sensitivity ET assay method. The changes in the cytokine production capacity of whole blood were also examined. We treated 24 peritonitis patients who had developed postoperative septic shock with ET adsorption therapy using a column of polymyxin B-immobilized fibers (PMX) and their serum ET levels were measured using the high-sensitivity ET assay based on the kinetic turbidimetric Limulus assay. In addition, the changes in the tumor necrosis factor-(TNF-alpha) production capacity of whole blood following lipopolysaccharide (LPS) stimulation and clinical outcome in the study patients were also examined. The 28-day mortality rate was 12%. PMX-direct hemoperfusion (PMX-DHP) was associated with elevation of the mean arterial pressure and urine output, reduction in the mean dose requirement of vasopressor agents, and recovery from the shock state in all the patients. The PaO2/FIO2 ratio also showed significant improvement. Using the high-sensitivity ET assay, ET was detected in the blood of 20 out of the 24 patients (80%) before the PMX-DHP, and a significant reduction in the ET level was noted after the PMX-DHP. The TNF-alpha production capacity of whole blood, which was found to be lower in the septic shock patients than in healthy subjects, was significantly increased after PMX-DHP. Elimination of ET by PMX-DHP in septic shock patients was confirmed by the high-sensitivity ET assay. PMX-DHP is thus considered to be a useful adjuvant therapeutic technique in the treatment of septic shock. Also, PMX-DHP might alleviate the immunosuppression associated with severe sepsis.

Adsorption↗
PubMed1991

[The role of endotoxin in the pathogenesis of bacterial peritonitis with special reference to superoxide in polymorphonuclear leukocytes stimulated by endotoxin].

It is well known that endotoxin (Et) plays an important role in severe surgical infectious diseases such as peritonitis. Recently, it has been reported that increased superoxide (O2-) formation and accelerated lipid-peroxidation cause the progress of Et shock. The present study was designed to estimate the changes in the amount of lipid-peroxides in the liver and the relationship between Et and lipid-peroxidation in bacterial peritonitis. Plasma Et levels, lipid-peroxides in the liver, the number of leukocytes in the blood and the number of bacteria in the blood and peritoneal cavity were determined using an experimental peritonitis model that was induced by intraperitoneal (i.p.) injection of E. coli, E. faecalis and B. fragilis, as well as experimental endotoxemia model induced i.p. injection of Et. The influence of ET on the function of polymorphonuclear leukocytes (PMN), that was considered to be one of the origins O2- production, was studied using PMN from the peritoneal cavity of rats. The plasma Et level was increased in an E. coli group and mixed injection group, and the lipid-peroxide levels in the liver were increased in these two groups as well as in a B. fragilis group. Plasma Et and lipid-peroxide levels in the liver were also increased in Et injected mice. In the study of the influence of Et on PMN function, O2- formation of PMN was increased when PMN was stimulated by Et with a high concentration and hexose monophosphate shunt activity was increased in all PMN stimulated by Et. These results suggest that O2- from PMN stimulated by Et is related to lipid-peroxidation in the liver, which is considered an index of injury in bacterial peritonitis.

Animals↗
PubMed2001

Glucan phosphate potentiates endotoxin-induced interferon-gamma expression in immunocompetent mice, but attenuates induction of endotoxin tolerance.

Glucan phosphate has been shown to enhance antimicrobial immunity in a variety of experimental models. However, the mechanisms by which glucans enhance resistance to infection remain largely unknown. Interferon-gamma (IFN-gamma) is a key regulator of both innate and acquired immunity. Suppression of IFN-gamma production is a prominent feature of the altered immune response that follows major trauma or sepsis. The present studies were designed to determine the effect of glucan phosphate on IFN-gamma expression in normal mice and endotoxin [lipopolysaccharide (LPS)]-tolerant mice. The model of LPS tolerance was used because it results in patterns of cytokine expression similar to those commonly observed following severe trauma or sepsis. Glucan treatment potentiated LPS-induced IFN-gamma expression in control mice. The induction of LPS tolerance resulted in marked suppression of LPS-induced IFN-gamma production. However, co-administration of glucan with LPS, during the tolerance induction phase, attenuated the LPS-tolerant response. Interleukin-12 (IL-12) and IL-18 are important mediators of LPS-induced IFN-gamma production. LPS-induced IL-12 p40 mRNA expression was increased in the spleens of glucan-treated mice compared with controls. Induction of LPS tolerance caused marked suppression of IL-12 production, a response that was attenuated by glucan treatment. IL-18 was constitutively expressed in both control and LPS-tolerant mice, and LPS-induced serum levels of IL-18 were increased in mice treated with glucan. T cells isolated from glucan-treated mice exhibited increased IFN-gamma expression in response to IL-12 and IL-18, as well as increased expression of the IL-12 and IL-18 receptors. The ability of glucan to potentiate IFN-gamma expression in control mice provides a potential mechanism by which glucan enhances antimicrobial immunity. The ability of glucan to attenuate suppressed IFN-gamma expression in LPS-tolerant mice denotes its potential benefit for the treatment of trauma and sepsis-induced immunosuppression.

Animals↗
PubMed1992

Endotoxin-induced cytokine gene expression in vivo. IV. Expression of interleukin-1 alpha/beta and interleukin-1 receptor antagonist mRNA during endotoxemia and during endotoxin-initiated local acute inflammation.

After the intravenous (IV) injection of endotoxin, (lipopolysaccharide [LPS]), in the rat, interleukin-1 alpha/beta (IL-1 alpha/beta) mRNA expression peaks at 1 hour in whole organ RNA preparations of the lung, liver, spleen, and bowel. Interleukin-1 receptor antagonist (IL-1ra) mRNA peaks at 2 to 4 hours, consistent with the hypothesis that IL-1ra acts as an endogenous negative feedback mechanism to downregulate the proinflammatory effects of IL-1. After the intratracheal (IT) injection of LPS, however, IL-1 and IL-1ra mRNA levels in whole lung peak at 6 hours, concurrent with the maximum influx of neutrophils (PMNs) into the bronchoalveolar space. To address the cellular source of IL-1 and IL-1ra mRNA in the lung during acute pneumonitis, mRNA levels were studied in bronchoalveolar lavage (BAL) macrophages incubated with LPS in vitro for 6 hours as compared with BAL cells (95% PMNs) obtained 6 hours after IT injection of LPS. A much greater expression of IL-1 and IL-1ra mRNA was observed in PMN-rich BAL cells obtained after IT injection of LPS, suggesting that PMNs contribute substantially to IL-1 and IL-1ra mRNA expression. Fractionation of alveolar macrophage-enriched and PMN-enriched subpopulations from the BAL cells obtained at 6 hours after IT injection of LPS confirmed that neutrophils are a source of IL-1 and IL-1ra mRNA. The difference in the kinetics of IL-1 and IL-1ra mRNA expression in whole lung RNA preparations after IV and IT injections of LPS is due to the contribution of PMNs that appear in the lung in large numbers after IT injection. Finally, human peripheral blood PMNs were found to express IL-1ra mRNA and protein after in vitro incubation with LPS. PMNs may contribute to the up- and downregulation of their own accumulation by expressing both IL-1 and IL-1ra.

Animals↗
PubMed1991

The intratracheal administration of endotoxin and cytokines. III. The interleukin-1 (IL-1) receptor antagonist inhibits endotoxin- and IL-1-induced acute inflammation.

Endotoxin, a lipopolysaccharide (LPS) component of gram-negative bacteria, induces alveolar macrophages to express interleukin-1 (IL-1). Lipopolysaccharide and IL-1 both cause severe acute neutrophilic inflammation in the lung after intratracheal injection, suggesting that LPS-induced IL-1 expression contributes to the pathogenesis of LPS-induced acute inflammation. In the present study, the role of IL-1 in LPS-induced acute pneumonia was investigated by quantitating the acute inflammation occurring at 6 hours after the intratracheal injection of LPS as compared to the same timepoint after the intratracheal coinjection of LPS and IL-1 receptor antagonist (IL-1ra). The IL-1ra was found to inhibit LPS-induced acute inflammation (P greater than 0.0001) as measured by the number of neutrophils recovered in bronchoalveolar lavage. The LPS-induced emigration of neutrophils was inhibited by as much as 45%. Recombinant IL-1 beta-induced neutrophil emigration into the lung was inhibited by 95% when IL-1ra was coinjected intratracheally with IL-1 beta. Coinjection of recombinant IL-1 beta and LPS increased the neutrophilic exodus as compared to the intratracheal injection of either agent alone. Intratracheal injection of LPS induces a progressive increase in IL-1ra mRNA expression in whole-lung RNA preparations, suggesting that endogenous IL-1ra may play an important role as a negative feedback mechanism to downregulate LPS initiated IL-1-mediated acute inflammation. In conclusion IL-1ra inhibits both LPS- and IL-1-induced neutrophilic inflammation and may therefore prove clinically useful as an anti-inflammatory agent for the therapy of either septic or aseptic IL-1-mediated acute inflammation.

Animals↗
PubMed1991

[Evaluation of the dose of endotoxin to produce endotoxin shock models in dogs].

Intravenous bolus administration of purified endotoxin (ET) is one of the most popular methods of producing experimental ET shock. In an attempt to evaluate the dose of ET in these experimental models, the kinetics of ET was assessed in various doses (1-0.002 mg.kg-1), and dose response study was performed, measuring chronological changes in hemodynamic (mean arterial pressure & cardiac output) and hematological (leucocyte & platelet counts) parameters. It was demonstrated that plasma ET concentrations were sustained extraordinarily high (greater than 5000 pg.ml-1) in doses of 0.2-1 mg.kg-1 during the observation period of several hours, while they were measurable in doses of 0.02 and 0.002 mg.kg-1, showing a biphasic decrease pattern after ET administration. In particular, plasma ET levels of low dose group (0.002 mg.kg-1) were similar to those of clinical gram negative septic patients. We conclude that the empirically used ET doses of more than 1 mg.kg-1 produce extremely severe endotoxemia and that milder degree of ET shock models produced by low dose of ET (0.002 mg.kg-1) would be more applicable for a pathophysiological study of ET shock.

Animals↗
PubMedDate not supplied

The effect of endotoxin and endotoxin tolerance on inflammation induced by mycobacterial adjuvant.

Peptidoglycan, the substance in mycobacteria thought to be responsible for inducing adjuvant arthritis, and endotoxin (lipopolysaccharide or LPS) share many inflammatory properties. Since repeated administration of LPS produces tolerance, i.e., resistance to the toxic and inflammatory effects of LPS, we tested whether LPS and/or LPS tolerance might influence inflammation due to mycobacterial adjuvant. Male Sprague-Dawley rats were injected with Escherichia coli LPS or saline intraperitoneally and then challenged with 100 micrograms killed Mycobacteria butyricum (adjuvant) in the footpad. A single dose of 100 micrograms LPS three or 24 hours before adjuvant markedly, but transiently, reduced the local footpad swelling that begins within hours of the adjuvant injection and histologically resembles a sterile abscess. Animals that received multiple doses of LPS and were therefore tolerant or animals that received LPS 72 hours before adjuvant demonstrated adjuvant-induced footpad swelling nearly equal to controls. The anti-inflammatory effect of LPS was transient since footpad swelling in all groups was nearly comparable six days after the adjuvant injection and LPS failed to inhibit consistently the arthritis that develops two or more weeks after adjuvant injection. These studies establish that LPS can markedly inhibit the prodrome of adjuvant arthritis (footpad swelling due to M. butyricum), that inhibition of this prodrome does not prevent the subsequent development of arthritis, and that LPS tolerance diminishes this anti-inflammatory effect of LPS.

Animals↗
PubMed1983

Interaction of latex-insolubilized endotoxins with murine macrophages: phagocytic responses of endotoxin-responsive (C3HeB/FeJ) and -unresponsive (C3H/HeJ) macrophages in vitro.

Insolubilized lipopolysaccharides (LPS) were prepared by covalently coupling LPS from polysaccharide-deficient S. minnesota R595 and polysaccharide-rich E. coli 055:B5 to carboxylated latex particles. The stability of these LPS-latex complexes was determined using several assays to detect soluble LPS following incubation at ambient and elevated temperatures. Resident and thioglycollate-elicited macrophages from both LPS-responder C3HeB/FeJ and LPS nonresponder C3H/HeJ mice were examined for their capacity to phagocytose the LPS particles following in vitro culture for various time periods. Uptake was demonstrated by an increase in the number of particles within the macrophages with increasing time of incubation. Rough polysaccharide-deficient LPS-latex particles were found to be more readily phagocytosed than control particles, whereas smooth polysaccharide-rich LPS particles were phagocytosed less readily than the controls. Qualitatively similar results were found in the relative rate of uptake of particles by the macrophages from the endotoxin-responsive and -unresponsive mouse strains used in this study.

Animals↗
PubMed1993

Endotoxin-induced expression of endotoxin binding sites on murine bone marrow cells.

A variety of binding sites for endotoxin (LPS) have been identified on leukocytes. However, the sequence of expression of these receptors, and their interrelations, are poorly understood. In this report, we show that in LPS-responsive hosts, interaction of nanomolar concentrations of LPS with bone marrow cells induces the expression of new specific LPS-binding sites. Cells from LPS-nonresponsive (C3H/HeJ) mice do not express these receptors after LPS treatment. Experimental differences in the conditions allowing the induction and the detection of these binding sites (influence of Leishmania lipophosphoglycan, role of serum), support the hypothesis that interaction of LPS with primary receptors on bone marrow cells triggers the expression of secondary LPS receptors, and that the two types of receptors have distinct fine specificities.

Animals↗
PubMed1993

Anti-endotoxin antibodies and other inhibitors of endotoxin.

Neutralization of endotoxin (lipopolysaccharide) would be of considerable benefit in the treatment of Gram-negative sepsis. Administration of anti-lipopolysaccharide antibodies is an old approach that has been renewed by improvements in monoclonal antibody technology. Experimental and clinical studies of antibodies directed at the conserved core region of lipopolysaccharide or at the lipid A are discussed. Some of these antibodies appear to be protective in animal models or in clinical trials, but discrepant results have been reported and the mechanism of the postulated protection was not clarified. Despite the availability of a monoclonal anti-lipid A antibody on the market in some European countries, this type of treatment should still be considered of unclear value until further experimental and clinical studies have reinvestigated the protection afforded by these antibodies. The use of detoxified lipid A analogs with lipopolysaccharide antagonist properties is another promising strategy that is discussed briefly in this review. Recently, substantial progress has been made in understanding how lipopolysaccharide triggers the immune system. A family of proteins possessing lipopolysaccharide-binding sites has been discovered. These proteins have a striking homology in DNA sequence, but they have different functions. The biological role of these proteins is now being actively investigated. New strategies to improve the outcome of Gram-negative sepsis may result from this research.

Animals↗
PubMed1993

Reduced response to intravenous endotoxin injections following repeated oral administration of endotoxin in the pig.

Three prepubertal gilts were each given 100 mg of endotoxin (ET) in their ordinary feed rations, twice daily for 6 days; 3 other gilts received standard feed. Following ET feeding, all animals were injected intravenously (i.v.) with ET (1.0 microgram/kg b.w.) once daily for 5 days. Blood samples were collected and analysed for hematology and total serum bile acids (S-BA), glutamate dehydrogenase (S-GLDH), calcium (S-Ca), iron (S-Fe), zinc (S-Zn) and a blood plasma metabolite (15-ketodihydro-PGF2a; P-PG) of prostaglandin F2a. The animals showed no apparent clinical symptoms following ET-feeding, neither did the blood analyses reveal effects of oral ET. However, when iv ET injections were given, the ET-fed animals showed fewer clinical signs of endotoxemia following the 2nd to 5th injection. S-BA and S-GLDH increased markedly in the standard-fed group following the first injection, while the ET-fed animals showed a much smaller increase in S-BA and no change in S-GLDH on that day. The difference in response may be explained by a direct uptake of ET from the gastrointestinal tract in the ET-fed pigs, making them less sensitive to the injected ET.

Administration, Oral↗
PubMed1997

Antagonism by ethanol of endotoxin-induced tissue factor activation in relation to the depressed endotoxin binding to monocyte-like U937 cells.

Our previous study has reported that ethanol (ETOH) partially inhibited the endotoxin (LPS)-induced tissue factor (TF)-activation in monocytes including blood peripheral monocytes as well as cultured leukemic U937 and THP-1 cells. The present study shows a strong correlation (r = 0.92; p < 0.01) between TF-activation and depression in LPS binding blocked by ETOH in U937 cells. The antagonism by ETOH of LPS binding was not due to a direct extracellular blockade, since ETOH did not affect the affinity of fluorescein isothiocyanate (FITC)-LPS or -anti CD14 mAb on U937 cells. After U937 cells were treated with 2 per cent (v/v) ETOH for 3 h, LPS binding was however drastically inhibited as shown by immunostaining with FITC-LPS which was viewed on a confocal laser scanning microscope. The results imply that cellular events of the ETOH effect mediate this inhibition of LPS binding. Anti-CD14 mAb (UCHM-1) inhibited LPS binding in a dose-dependent fashion, revealing a competitive specific binding to the LPS receptor. The results suggest that CD14 plays an important role in the recognition of LPS. FITC-UCHM-1 binding was significantly reduced in the cells pretreated with 2 per cent (v/v) ETOH for 3 h, indicating that ETOH modulates the ability to express CD14. CD14 expression was upregulated by priming with LPS which was offset by ETOH. Acetaldehyde, a possible metabolite of ETOH, was tested with no effect on CD14 expression. Taken together, our results show that ETOH downregulates the recognition of LPS, and suggest that the inhibitory action is likely to be mediated by the depression in CD14 expression which was also accompanied by a significantly altered membrane fluidity. Thus, the antagonism by ETOH of the binding of LPS results in a depression in the LPS-induced TF-activation.

Anti-Infective Agents, Local↗
PubMed1998

Endotoxin activation of mitogen-activated protein kinase in THP-1 cells; diminished activation following endotoxin desensitization.

The signal transduction events occurring in monocytes in response to endotoxin (LPS) stimulation are incompletely delineated, although pertussis toxin (PT)-sensitive G proteins and the mitogen-activated protein kinase (MAPK) cascade have been implicated. Cellular desensitization in response to 18-h pre-exposure to 1 microgram/mL LPS alters signal transduction pathways of cellular activation and decreases production of certain inflammatory mediators such as thromboxane (Tx)B2, the stable metabolite of TxA2. We hypothesized that LPS stimulation of the human monocyte cell line THP-1 occurs via MAPK activation, and that LPS desensitization, induced by pre-exposure to LPS, is associated with altered signaling through the MAPK cascade. Involvement of a specific MAPK, ERK, in LPS-stimulated TxB2 production was further tested using a specific MAPK cascade inhibitor, PD98059 (PD). PD inhibited LPS and phorbol myristate acetate (PMA)-stimulated ERK activation as demonstrated by immunoblots using anti-activated ERK antibodies. PD significantly inhibited LPS and PMA-stimulated TxB2 synthesis to non-detectable levels, suggesting an involvement of MAPK in LPS-stimulated activation. Because PT-sensitive G proteins mediate LPS-stimulated signal transduction, their role in MAPK activation was tested. Pretreatment with PT inhibited basal and LPS-stimulated, but not PMA-stimulated ERK activation. Activation of ERK after LPS desensitization was also assessed. LPS pre-exposure resulted in a profound decrease in LPS-stimulated activation of ERK, but did not affect PMA activation of ERK. These data implicate the involvement of the MAPK cascade in LPS-stimulated activation of THP-1 cells and suggest coupling of Gi proteins and MAPKs in LPS-stimulated events. LPS desensitization is associated with decreased MAPK activation, but does not impair MAPK activation by PMA. Thus, LPS desensitization appears to selectively alter signal transduction upstream of ERK.

Carcinogens↗
PubMedDate not supplied

Endotoxin tolerance: regulation of cytokine production and cellular changes in response to endotoxin application in cancer patients.

Endotoxin (lipopolysaccharide, LPS) has the property of inducing tolerance to its own biological effects. This phenomenon has been extensively studied in animal models but only few studies exist on the regulation in humans. Here we describe experiments designed to determine the cytokine regulation and cellular changes in humans during induction of LPS tolerance after repeated LPS injections. Intravenous administration of purified LPS Salmonella abortus equi to cancer patients induces high amounts of circulating tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-8 (IL-8), granulocyte colony-stimulating factor (G-CSF), and macrophage colony-stimulating factor (M-CSF). Repeated injections of LPS at daily intervals resulted in a marked downregulation of the cytokine response and in the case of TNF-alpha, IL-8, G-CSF, and M-CSF the cytokine response was reduced to baseline levels. In contrast, significant increases in serum IL-6 were detected up to day 5 of repeated LPS injections. Hematological changes included transient decreases in WBCs affecting granulocytes, monocytes, and lymphocytes, followed by a marked granulocytosis. The drop in WBCs remained unaltered throughout the 5 day course of repeated LPS injections whereas the granulocyte overshoot recovery diminished gradually. When PBMCs of the cancer patients were restimulated ex vivo a marked enhancement of the capacity to produce TNF-alpha, IL-113, and IL-6 occurred, which is in contrast to the decreasing TNF-alpha serum levels obtained in vivo. In parallel, a shift in monocyte subpopulations from CD14+/CD16- to CD14+/CD16+ cells was observed. The data provide evidence that different mechanisms are implicated in the cytokine downregulation following repeated LPS injections to cancer patients. Furthermore, PBMCs from LPS tolerant patients do not demonstrate a reduction in their capacity to produce cytokines.

Antigens, CD↗
PubMedDate not supplied

[Effect of Escherichia coli endotoxin on thymus-dependent activation of T-immunity system and expression of lymphocyte endotoxin receptors in adolescents with reccurent bronchitis].

Endotoxin-dependent direct inhibition of functional activity of T-cell immunity and biological activity of thymus factors was revealed in patients with recurrent chronic bronchitis and with systemic endoxinemia. The findings are considered by authors as an important pathogenetic mechanism inhibiting stable regression of inflammation in bronchopulmonary system in juvenile patients with recurrent chronic bronchitis. The correction of systemic endoxinemia in such patients is pathophysiologicaly substantiated.

Bronchitis↗
PubMed1995

Radiodetoxified endotoxin-induced tolerance. Effect on endotoxin lethality and macrophage arachidonic acid metabolism.

Endotoxin (LPS) tolerance produces changes in macrophage mediator production which is thought to be responsible for the acquired LPS resistance. Detoxification of LPS by gamma irradiation has been reported to diminish certain noxious properties while retaining its tolerance inducing actions. We compared the efficacy of LPS and radiodetoxified (RD)-LPS from Escherichia coli O101 on stimulating rat peritoneal macrophage arachidonic acid (AA) metabolism, measured by thromboxane (TXB2). Changes in macrophage production of these mediators were also assessed after tolerance induction. LPS tolerance was induced by i.p. injection of LPS, RD-LPS or vehicle on day 1 (100 micrograms/kg, i.p.) and day 2 (500 micrograms/kg, i.p.). On day 5 or 4 weeks after pretreatment, peritoneal macrophages were harvested for in vitro studies, or rats were tested for lethality resistance. Macrophages were incubated +/- LPS (0.1 ng to 50 micrograms/ml), lipid A (1 or 10 micrograms/ml) or Ca+2 ionophore A23187 (10 microM) for determination of TXB2 production. Minimum effective concentrations of LPS and RD-LPS for stimulation (P < 0.05) of TXB2 were 100 ng/ml and 1 microgram/ml, respectively. Maximal stimulation of TXB2 occurred at 10 micrograms/ml of LPS or RD-LPS. Macrophages from LPS or RD-LPS tolerized rats were refractory to stimulated TXB2 with LPS or RD-LPS (0.1 ng to 50 micrograms/ml). The suppressed in vitro macrophage TXB2 production was apparent 4 weeks after rats were tolerized with LPS or RD-LPS. In subsequent mortality studies, LPS challenge of control or tolerance rats at day 5 in vivo with Salmonella enteritidis LPS (15 mg/kg, i.v.) produced a 90% mortality in control rats (N = 22), versus 13% mortality in the LPS pretreated group (N = 23) and a 20% in the RD-LPS pretreated group (N = 10) (P < 0.05 vs control). However, this lethality resistance was not apparent at 4 weeks after LPS or RD-LPS pretreatment. Both LPS and RD-LPS appear to be equipotent in inducing macrophage alterations, and in lethality resistance during LPS tolerance induction. However, these observations suggest that during LPS tolerance suppression of LPS-stimulated AA in peritoneal macrophage metabolism persists longer than acquired lethality resistance.

Animals↗