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PubMed2005

Inhibition by nitric oxide of cytochrome P450 4A activity contributes to endotoxin-induced hypotension in rats.

Nitric oxide (NO) production during endotoxemia is associated with decreased total CYP content, CYP 1A1/2, 2B1/2, 2C6, 2C11, 3A1, and 3A2 mRNA, protein expression or activity which is prevented by NO synthase (NOS) inhibitors in rats. This study was conducted to determine if endotoxin-induced hypotension caused by NO production is mediated by inhibition of renal CYP 4A protein expression and activity. In conscious male Sprague-Dawley rats, endotoxin (10 mg/kg, ip) reduced mean arterial pressure (MAP), increased serum and renal nitrite levels, and inducible NOS (iNOS), and decreased renal CYP 4A1/A3 protein and CYP 4A activity. The selective iNOS inhibitor 1,3-PBIT (10 mg/kg, ip; 1h after endotoxin) prevented endotoxin-induced decrease in MAP, renal CYP 4A1/A3 protein level and CYP 4A activity and increase in systemic and renal nitrite production. The selective constitutive NOS (cNOS) inhibitor N(G)-nitro-L-arginine (L-NNA; 20 mg/kg, ip; 1 h after endotoxin) partially attenuated endotoxin-induced decrease in MAP. The selective CYP 4A inhibitor, aminobenzotriazole (50 mg/kg, ip; 1 h after endotoxin) diminished CYP 4A1/A3 protein level and CYP 4A activity. Aminobenzotriazole did not alter the endotoxin-induced decrease in MAP, but it reversed the effect of 1,3-PBIT in preventing endotoxin-induced fall in MAP and CYP 4A activity. These data suggest that the endotoxemia-induced increase in NO production primarily via iNOS suppresses renal CYP 4A expression and activity, and inhibition of iNOS with 1,3-PBIT restores renal CYP 4A protein and activity and MAP presumably due to increased production of arachidonic acid metabolites derived from CYP 4A.

Animals↗
PubMed2002

Pathophysiologic quantities of endotoxin-induced tumor necrosis factor-alpha release in whole blood from patients with chronic heart failure.

Bacterial endotoxin activity is elevated in patients with decompensated chronic heart failure (HF) and acts as a potent stimulus for immune activation. We sought to determine whether endotoxin, at an activity level seen in vivo (around 0.6 EU/ml), is sufficient to stimulate the secretion of tumor necrosis factor-alpha (TNF-alpha) and TNF-alpha soluble receptor (sTNFR2) in ex vivo whole blood from patients with HF. We studied 15 patients with HF (aged 65 +/- 1.9 years, New York Heart Association class 2.1 +/- 0.3, left ventricular ejection fraction 31 +/- 5%; mean +/- SEM), of whom 5 had cardiac cachexia, and 7 healthy control subjects (59 +/- 5 years, p = NS). Reference endotoxin was added to venous blood at concentrations of 0.6, 1.0, and 3.0 EU/ml, and was incubated for 6 hours. Endotoxin induced a dose-dependent increase in TNF-alpha release (p <0.05 in all groups). Patients with noncachectic HF produced significantly more TNF-alpha compared with controls after stimulation with 0.6, 1.0, and 3.0 EU/ml of endotoxin (113 +/- 46 vs 22 +/- 4 [p = 0.009], 149 +/- 48 vs 34 +/- 4 [p = 0.002], and 328 +/- 88 vs 89 +/- 16 pg/ml [p = 0.002], respectively; mean +/- SEM). Patients with cardiac cachexia produced significantly less TNF-alpha compared with patients without cardiac cachexia for all given concentrations (all p <0.05, analysis of variance p = 0.02). Production of sTNFR2 was greater at all concentrations of endotoxin versus controls (all p <0.05, analysis of variance p = 0.002). Plasma endotoxin levels were higher in patients with cardiac cachexia (4.3 times higher than in control subjects, p <0.005). Thus, low endotoxin activity, at levels seen in vivo in patients with HF, induces significant TNF-alpha and sTNFR2 production ex vivo. These results suggest that elevated plasma endotoxin activity observed in patients with HF is of pathophysiologic relevance.

Adult↗
PubMed1997

Removal of endotoxin from recombinant protein preparations.

OBJECTIVES: To develop an effective method to remove endotoxin from large scale E. coli recombinant protein purifications. DESIGN AND METHODS: Triton X-114 phase separation, affinity chromatography utilizing immobilized polymyxin B or immobilized histidine, were used to remove endotoxin from purified preparations of recombinant CK-BB, CK-MB, CK-MM, myoglobin, and cardiac troponin I. Endotoxin levels were measured by a Limulus Amebocyte Lysate gel-clot assay. The immunoactivity of these protein preparations was determined by BIAcore analysis using a panel of in-house generated monoclonal antibodies and by a Stratus Fluorometric Analyzer. In the case of troponin I, the BIAcore was also utilized to measure troponin C interactions. RESULTS: Phase separation with Triton X-114 was the most effective method in reducing the amount of endotoxin present in the protein preparations compared to either polymyxin B or histidine affinity chromatography. With Triton X-114, the reduction in endotoxin levels was greater than 99% and recovery of the proteins after endotoxin removal was greater than 90%. All three procedures for removing endotoxin had no deleterious effects on the immunoactivity of majority proteins when tested with a panel of monoclonal antibodies. Troponin I also retained its ability to bind to troponin C in the presence of Ca2+. Recombinant CK-BB and CK-MM which were expressed in the soluble fraction of E. coli cell lysates, contained significantly higher endotoxin levels than recombinant CK-MB, myoglobin and cardiac troponin I which were expressed in the form of inclusion bodies. CONCLUSION: Of the three methods tested, Triton X-114 phase separation was the most effective way of removing endotoxin from recombinant proteins.

Biochemistry↗
PubMed2002

Effect of endotoxin on doxorubicin transport across blood-brain barrier and P-glycoprotein function in mice.

The aim of this study was to investigate whether Klebsiella pneumoniae endotoxin modifies transport of doxorubicin, a P-glycoprotein substrate, across the blood-brain barrier and P-glycoprotein function in mice. Doxorubicin (30 mg/kg) was administered into the tail vein or fluorescein isothiocyanate-labeled dextran (FD-4) was infused (20 microg/min) into the right jugular vein of mice intravenously injected with endotoxin (10 mg/kg) 6 or 24 h earlier. Blood and brain samples were collected 4 h after injection of doxorubicin or 1 h after infusion of FD-4. We examined using Western blotting the influence of endotoxin on the expression of P-glycoprotein in brains obtained 6, 12 and 24 h after injection. Endotoxin did not change the plasma and brain concentrations and brain-to-plasma concentration ratio (K(p) value) of FD-4. No histopathological changes in brain capillaries were observed. These results suggest that endotoxin does not cause damage to brain capillaries. Plasma and brain concentrations of doxorubicin in mice treated 6 h earlier with endotoxin were significantly higher than those in control and mice treated 24 h earlier. However, endotoxin did not significantly change the K(p) value of doxorubicin. The protein level of P-glycoprotein was significantly, but slightly down-regulated 6 h after endotoxin treatment. However, the levels remained almost unchanged after 12 and 24 h. The present results suggest that Klebsiella pneumoniae endotoxin has no effect on the brain capillary integrity and doxorubicin transport across the blood-brain barrier in mice. It is likely that P-glycoprotein function might be sufficient to transport doxorubicin in spite of decreased levels of P-glycoprotein in the brain.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Effects of neuropeptide FF on intestinal motility and temperature changes induced by endotoxin and platelet-activating factor.

Several effects of bacterial endotoxins involve an opioid pathway and neuropeptide FF is an endogenous peptide known to modulate opioid activity, mainly in the central nervous system. The aim of this study was to investigate in rats the role of central neuropeptide FF receptors in intestinal motor disturbances and body temperature changes induced by endotoxins and platelet-activating factor (PAF), a major endotoxin mediator. Rats were fitted with intestinal electrodes, an intraperitoneal thermistor probe and an intracerebroventricular (i.c.v.) cannula for long-term use. E. coli endotoxin (100 microg/kg, i.v.) disrupted the cyclic pattern of intestinal migrating myoelectric complexes and induced a biphasic increase in body temperature while PAF (25 microg/kg, i.p.) disrupted the migrating myoelectric complexes and induced hypothermia for about 2 h. The neuropeptide FF analog, (1 DME)Y8Fa (D-Tyr-D-Leu[N-Me]-Phe-Gln-Pro-Gln-Arg-Phe-NH2) administered i.c.v. 40 and 100 microg/kg reduced the duration of migrating myoelectric complex disruption induced by endotoxin and PAF and abolished the PAF-induced hypothermia. Only at the dose of 100 microg/kg did (1 DME)Y8Fa change the biphasic endotoxin-induced hyperthermia into a monophasic increase. Naloxone (1 mg/kg, s.c.) reduced only the duration of migrating myoelectric complex disruption induced by endotoxin. These results indicate that central neuropeptide FF modulates the intestinal motor disturbances and changes in body temperature induced by endotoxin and PAF. Its action against endotoxin may involve an anti-opioid pathway whereas its action against PAF does not.

Animals↗
PubMed2003

Endotoxin impairs endothelium-dependent vasodilation more in the coronary and renal arteries than in other arteries of the rat.

Endotoxemia may result in endothelial dysfunction, and some vascular beds may be affected more than others. To test this hypothesis, we studied, in vitro, the reactivity of isolated rat coronary, renal, superior mesenteric, and hepatic arteries exposed to endotoxin (E. coli, 50 microg. mL(-1)) or saline for 2 h at 37 degrees C. Vascular smooth muscle function was tested using 125 mM KCl, the vasoconstrictors norepinephrine (NE), and the thromboxane analog U46619 (coronary artery). Endothelium-dependent vasorelaxation was tested with acetylcholine (ACh) in preconstricted vessels. Although differing between vessel types, the smooth muscle contractile responses were not affected by endotoxin, either in the presence or absence of L-arginine. Endotoxin impaired the response to ACh in rat coronary arteries (92.7 +/- 4.6% vasodilation in control and 41.3 +/- 11.6% in endotoxin-exposed segments) and in renal arteries (66.7 +/- 5.2% vasodilation in control and 43.2 +/- 4.9% in endotoxin-exposed segments), so that there was a mean 55% decrease vs controls in coronary and a mean 35% decrease in renal arteries. Endotoxin did not affect superior mesenteric and hepatic arteries. Brief endotoxin exposure of isolated rat arteries may thus inactivate endothelial NO synthase, independent of iNOS. The increase in heterogeneity among endothelium-dependent vasodilation after endotoxin may help to explain early blood flow maldistribution in endotoxin shock.

Animals↗
PubMed1998

Effects of various doses of antithrombin III on endotoxin-induced endothelial cell injury and coagulation abnormalities in rats.

We previously demonstrated that antithrombin III reduced the injury to endothelial cells caused by activated leukocytes in rats administered endotoxin. This occurred via the increase of the endothelial release of prostaglandin I2, which is a potent inhibitor of leukocyte activation. We evaluated the dose of antithrombin III required to prevent such endothelial cell injury in rats administered endotoxin, by comparing the effects of various antithrombin II doses on the pulmonary vascular injury. The intravenous administration of endotoxin, 5 mg/kg, produced a transient accumulation of leukocytes in the lung, followed by pulmonary vascular injury, as indicated by an increase in the pulmonary vascular permeability, and coagulation abnormalities. The dose of 250 U/kg significantly inhibited all such effects of endotoxin. While lower doses of antithrombin III (50 and 100 U/kg) significantly inhibited such coagulation abnormalities, they failed to prevent either the pulmonary accumulation of leukocytes or the subsequent pulmonary vascular injury. Rats administered endotoxin exhibited an accumulation of neutrophils and edematous changes in the pulmonary interstitial space. Although such changes were reduced after 250 U/kg of antithrombin III, they were unaffected by lower doses of 50 and 100 U/kg. Plasma levels of 6-keto-PGF1alpha were markedly increased in rats 90 min after the administration of endotoxin, and were significantly decreased in the endotoxin-treated rats administered the lower doses of antithrombin III (50 and 100 U/kg), but not altered in those endotoxin-treated rats receiving 250 U/kg of antithrombin III. These findings suggest that a higher antithrombin III dose is necessary to prevent endothelial cell injury than is required to inhibit coagulation abnormalities in an animal model of sepsis. These observations support the notion that antithrombin III may prevent endotoxin-induced endothelial cell injury by promoting endothelial release of prostaglandin I2 and thus inhibiting leukocyte activation.

6-Ketoprostaglandin F1 alpha↗
PubMed2000

Relation between house-dust endotoxin exposure, type 1 T-cell development, and allergen sensitisation in infants at high risk of asthma.

BACKGROUND: Bacterial endotoxin is known to induce interferon gamma and interleukin 12 production, and therefore has the potential to decrease allergen sensitisation. To find out the role of early chronic endotoxin exposure in the development of allergen sensitisation and asthma, we compared concentrations of endotoxin in house dust with allergen sensitisation in infants at high risk for developing asthma. METHODS: 61 infants 9-24 months old with at least three physician-documented episodes of wheezing were studied. Concentrations of house-dust endotoxin and allergens were measured in the infants' homes. Allergen sensitisation was measured by skin-prick testing with a panel of common inhalant and food allergens. In a subset of these infants, proportions of T lymphocytes producing interferon gamma, and interleukins 4, 5, and 13 were calculated by cell-surface and intracellular cytokine staining, with flow cytometry. FINDINGS: House-dust endotoxin concentrations ranged from 104 to 10,000 endotoxin units (EU) per mL (geometric mean 912 EU/mL). Concentrations did not vary significantly over a 6-month interval. Ten infants (16%) were sensitised to at least one allergen. The homes of allergen-sensitised infants contained significantly lower concentrations of house-dust endotoxin than those of non-sensitised infants (mean 468 vs 1035 EU/mL, respectively; p=0.01). Increased house-dust endotoxin concentrations correlated with increased proportions of interferon-gamma-producing CD4 T cells (p=0.01). Such concentrations did not correlate with proportions of cells that produced interleukins 4, 5, or 13. INTERPRETATION: This study may provide the first direct in-vivo evidence that indoor endotoxin exposure early in life may protect against allergen sensitisation by enhancing type 1 immunity.

Allergens↗
PubMed2000

Endotoxin removal from protein solutions.

Endotoxins liberated by gram-negative bacteria are frequent contaminations of protein solutions derived from bioprocesses. Because of their high toxicity in vivo and in vitro, their removal is essential for a safe parenteral administration. A general method for the removal of endotoxins from protein solutions is not available. Methods used for decontamination of water, such as ultrafiltration, have little effect on endotoxin levels in protein solutions. Various techniques described in the patent literature are not broadly applicable, as they are tailored to meet specific product requirements. Besides ion-exchangers and two-phase extraction, affinity techniques are applied with varying success. Also, taylor-made endotoxin-selective adsorber matrices for the prevention of endotoxin contamination and endotoxin removal are discussed for this purpose. After giving an overview of the properties of endotoxins and the significance of endotoxin contamination, this review intends to provide an overall picture of the various methods employed for their removal. Avenues are pointed out how to optimise a method with regard to the specific properties of endotoxins in aqueous solution.

Adsorption↗
PubMed2001

Adsorption of endotoxins on glass in the presence of cationic proteins.

Endotoxin activity was detected in empty glass tubes where endotoxins were incubated with lysozyme, histone or RNaseA, indicating adsorption of endotoxins on glass in the presence of cationic proteins. In the case of lysozyme, the recovery of spiked endotoxins (90.0%) using polystyrene tubes for incubation was much greater than the recovery (28.5%) using glass tubes, suggesting that lysozyme-mediated adsorption of endotoxins on glass is a major cause of poor recovery of spiked endotoxins in the LAL assay using glass tubes. In contrast, the recovery of spiked endotoxins (64.7%) using polystyrene tubes in the presence of the non-cationic protein BSA was less than the recovery (103.9%) using glass tubes. The difference in endotoxin recovery using glass or polystyrene tubes in the presence of cationic proteins or BSA can be explained by differences in protein adsorption on the tubes. Consequently, care must be exercised in selecting containers used for the LAL assay of proteins which bind to endotoxins.

Adsorption↗
PubMed2002

Regulation of the growth hormone and luteinizing hormone response to endotoxin in sheep.

Infectious disease processes cause physiological adaptations in animals to reorder nutrient partitioning and other functions to support host survival. Endocrine, immune and nervous systems largely mediate this process. Using endotoxin injection as a model for catabolic disease processes (such as bacterial septicemia), we have focused our attention on regulation of growth hormone (GH) and luteinizing hormone (LH) secretion in sheep. Endotoxin produces an increase in plasma GH and a decrease in plasma LH concentrations. This pattern can be reproduced, in part, by administration of various cytokines. Antagonists to both interleukin-1 (IL-1) and tumor necrosis factor (TNF) given intravenously (IV) prevented the endotoxin-stimulated increase in GH. Since endotoxin will directly stimulate GH and LH release from cultured pituitary cells, the data suggest a pituitary site of action of the endotoxin to regulate GH. Studies with portal vein cannulated sheep indicated that gonadotropin releasing hormone was inhibited by endotoxin, suggesting a central site of action of endotoxin to regulate LH. However, other studies suggest that endotoxin may also regulate LH secretion at the pituitary. Thus, IL-1 and TNF regulate GH release from the pituitary gland while endotoxin induces a central inhibition of LH release.

Animals↗
PubMed2005

The role of endotoxin and its receptors in allergic disease.

OBJECTIVE: To summarize the existing literature on the association of endotoxin with respiratory diseases and allergic sensitization and to review the potentially modifying effects of endotoxin receptor polymorphisms. DATA SOURCES: English-language articles were identified from the MEDLINE and PubMed databases using combinations of the following search terms: endotoxin, toll-like receptor, polymorphisms, atopy, asthma, and allergy. Other sources included experts in the field and the bibliographies of pertinent articles. STUDY SELECTION: Relevant articles were selected based on the authors' expert opinion. RESULTS: Cross-sectional studies, particularly those of children raised in rural European communities, suggest that early endotoxin exposure may protect against the development of allergic sensitization and atopic asthma. However, endotoxin exposure may also contribute to other nonatopic respiratory disorders and may exacerbate disease in individuals with preexisting asthma. Paradoxically, among individuals exposed to high levels of endotoxin, carriers of a functional mutation in toll-like receptor 4, which reduces cellular responsiveness to endotoxin, may be at lower risk of developing allergic sensitization. CONCLUSIONS: The effect of endotoxin exposure on allergic sensitization and asthma appears to be influenced by the timing of exposure, the presence or absence of preexisting disease, and polymorphisms in the genes that encode endotoxin receptors. Further studies are needed to define the window period for this effect, as well as the underlying immunologic mechanism.

Asthma↗
PubMed2000

Effect of anti-asthmatic drugs on the response to inhaled endotoxin.

BACKGROUND: Endotoxin is a pro-inflammatory agent contaminating the dust that has been associated with the risk to develop pulmonary diseases. There is no data on the protective efficacy of anti-asthmatic drugs on the response induced by inhaled endotoxin in human. METHODS: Twelve mildly asthmatic subjects were submitted weekly to bronchial challenge tests with 20 microg endotoxin. The response was evaluated by the changes in FEV1, blood cells count, neutrophils activation (measured with the luminol-enhanced chemiluminescence) and blood concentration in the acute phase proteins, C-reactive protein (CRP) and haptoglobin. In a double-blind randomized cross-over placebo-controlled design, a single dose each of 500 microg beclomethasone dipropionate, 200 microg salbutamol, and 50 microg salmeterol were administered 30 minutes before the endotoxin challenge test. RESULTS: The 20-microg endotoxin challenge test induced a significant decrease in FEV1 and luminol-enhanced chemiluminescence (P < .001 and <.05, respectively). There was an increase in the blood neutrophils count (P < .05), in CRP (P < .02) and in haptoglobin (P < .03) concentrations. Pretreatment with beclomethasone dipropionate did not have any significant effect on the response to inhaled endotoxin. Salbutamol and salmeterol completely prevent the FEV1 decline due to their potent bronchodilatation activity. Salmeterol and salbutamol did not have any significant effect on the blood inflammation induced by endotoxin inhalation. CONCLUSION: The bronchodilating properties of beta2-agonists prevent the lung function response to inhaled endotoxin. When given in a single dose, an inhaled corticosteroid does not have protective activity on the endotoxin-induced blood inflammation.

Administration, Inhalation↗
PubMed2004

Something old, something new: indoor endotoxin, allergens and asthma.

Endotoxin and allergen exposure have been explored in the context of asthma for more than a century. Building upon a pyramid of knowledge are recent observations that provide new insights to the effect of these exposures on the development of asthma. Some of these studies challenge some previously held concepts of the role of these exposures in asthma inception. Indoor allergens are well established as the basis of inflammation in sensitised asthmatics, contributing to disease severity. Then does greater exposure to indoor allergens cause allergen sensitisation and asthma as well? While risk of sensitisation to house dust mites generally increases with higher levels of exposure, this does not seem to hold for cats, where higher levels of cat allergen exposure are associated with less sensitisation. Indeed, several recent studies suggest that early childhood exposure to animals, as indoor pets or in farming stables, are associated with a lower prevalence of asthma, hay fever, and inhalant allergen sensitisation. Endotoxin in asthma provides a similar paradox. Endotoxin is a potent immune-stimulatory component of the bacterial cell wall of all gram-negative bacteria. As such, endotoxin is ubiquitous in our environment. Endotoxin exposure has been well demonstrated to underlie "Monday Asthma" or byssinosis in cotton workers, and has since emerged as a frequent cause of asthma-like symptoms in a wide range of occupational settings. Asthmatics are particularly sensitive to inhaled endotoxin, and inhalation induces both immediate and sustained airflow obstruction. The paradox of endotoxin exposure is that higher levels of exposure in early life might mitigate the development of allergy and persistent asthma. With endotoxin exposure being significantly higher in homes with animals and in farming households, where allergy and asthma are less likely to develop, endotoxin and other microbial exposures in early life may keep allergen sensitisation and asthma from developing by promoting Th1-type immune development. These observations, consistent with the "Hygiene Hypothesis" of allergy and asthma, are an encouraging glimpse of the potential for early immune modulatory approaches to asthma therapy and prevention.

Air Pollution, Indoor↗
PubMed2000

Lack of endotoxin tolerance with respect to TNF alpha production in the subarachnoid space.

To study endotoxin tolerance in the subarachnoid space 0.1 mg of endotoxin derived from Neisseria meningitidis was injected intracisternally into rabbits on 2 consecutive days. On day 1 the maximum peak level of TNF alpha was 7 ng/ml 2 h after injection, whereas on day 2 the highest levels were 3.6 ng/ml and 3.7 ng/ml, respectively, 1 and 2 h after injection. Pretreatment with intravenous endotoxin 5 or 21 h before consecutive intracisternal endotoxin did not affect the cerebrospinal fluid (CSF) levels of TNF alpha. In contrast, there was a marked endotoxin tolerance with respect to TNF alpha in the systemic circulation. Cells appearing in the CSF 5, 12 and 20 h after intracisternal injection of endotoxin were harvested, cultured, and then stimulated with 0.1 mg/ml of endotoxin. In 10 experiments a marked TNF alpha production in the range 10-70 ng/ml was detected in the supernatants, whereas unstimulated cells did not produce TNF alpha. We conclude that tolerance to endotoxin does not develop in the subarachnoid space as evaluated by the present experimental design. The pattern of TNF alpha production and endotoxin tolerance is distinctly different in the subarachnoid space and systemic circulation.

Animals↗
PubMed2000

Characterization and variability of endotoxin and 3-hydroxy fatty acids in an office building during a particle intervention study.

Air and dust samples were collected on two floors of an office building during a double-blind particle intervention study to examine spatial and temporal variability of airborne endotoxin over a period of weeks, and to characterize endotoxin activity and lipopolysaccharide (LPS) content in carpet and chair dust. Air samples were collected on multiple days within and across weeks. Dust samples were collected from carpets and chairs one day per week for three weeks. Endotoxin was measured using a Limulus assay. Dust samples were analyzed for LPS by determination of 3-hydroxy fatty acids (3-OHFAs) using gas chromatography-mass spectrometry. The geometric mean (geometric standard deviation) for 96 indoor air samples was 0.24 (1.6) EU/m3. Significant within-floor spatial variation of airborne endotoxin was found (P < 0.0001, n = 80). Temporal variability of airborne endotoxin was not significant across weeks. Mean (+/- SD) endotoxin levels in carpet dust (59 +/- 9.3 EU/mg dust, n = 12) and in chair dust (38 +/- 7.7 EU/mg dust, n = 10) were significantly different (P < 0.001). Carbon chain length-dependent differences in 3-OHFA levels by dust source and floor were found. Enhanced air filtration did not significantly affect airborne endotoxin (P = 0.62); however, total dust mass and total endotoxin in carpet dust samples increased significantly after enhanced surface cleaning (P < 0.01). These findings suggest that spatial variability, dust source, and surface cleaning may influence building occupant exposures to endotoxin.

Air Pollution, Indoor↗
PubMed1987

Endotoxin provocation of experimental renal cystic disease.

Germ free rats provide a unique model in which to assess biological response to environment. In 48 germ-free male, Sprague-Dawley rats we examined the consequences of oral exposure to nordihydroguaiaretic acid (NDGA), a nephrotoxin; to Staphylococcus epidermidis and bacillus species, non-endotoxin-containing bacteria; to Escherichia coli and Proteus mirabilis, endotoxin-containing bacteria; and injected E. coli endotoxin on peripheral leukocyte counts and renal morphology. Morphological changes were evaluated by light microscopy and scored blindly on a 0 to 4+ scale for 15 parameters of renal structure. Means of these renal "pathology scores" correlated with counts of polymorphonuclear leukocytes and lymphocytes in the peripheral blood. The highest counts and scores were found in rats given NDGA and exposed to endotoxin, either by injection or by oral feeding of endotoxin-containing bacteria. Counts and scores were lower in the absence of endotoxin and with non-endotoxin-containing bacteria, given alone or in combination with either NDGA or endotoxin. Results exclude bacterial colonization and intrarenal accumulation of NDGA as causes of nephropathy. They indicate that endotoxin and NDGA act synergistically to provoke renal damage in the germ free NDGA-fed rat and suggest that leukocytes are involved in the process.

Animals↗
PubMed2001

A cerebral nitrergic pathway modulates endotoxin-induced changes in gastric motility.

1. This study analyses the neural pathway involved in the modulation of gastric motor function by stress. 2. Systemic administration of low doses of endotoxin (40 microg kg(-1), i.v.) prevents the increase in gastric tone induced by 2-deoxy-D-glucose (200 mg kg(-1), i.v., 2-DG) in urethane-anaesthetized rats. 3. Functional inhibition of afferent neurones by systemic administration of capsaicin (20+30+50 mg kg(-1), i.m.) in adult rats prevented the inhibitory effects of endotoxin. 4. Pre-treatment with the nitric oxide synthase (NOS) inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), both i.v. (10 mg kg(-1)) and i.c. (200 microg rat(-1)), prevented the inhibitory effects of endotoxin on gastric tone induced by 2-DG. 5. Immunohistochemical studies show Fos expression in the dorsal vagal complex (DVC) of the brainstem of 2-DG-treated animals. Peripheral administration of endotoxin (40 microg kg(-1), i.p.) increased the number of Fos-immunoreactive cells induced by 2-DG, both in the nucleus tractus solitarii (NTS) and in the dorsal motor nucleus (DMN) of the DVC. Pre-treatment with L-NAME prevented the increase in Fos expression induced by endotoxin in both nuclei. 6. Endotoxin (40 microg kg(-1), i.p.) increased Ca(2+)-dependent nitric oxide synthase (cNOS) activity in the brainstem. Addition of 7-nitroindazole (600 microM, 7-NI) to the assay significantly inhibited the increase in cNOS activity caused by endotoxin. No change in NOS activity of any isoform was observed in the stomach of animals treated with endotoxin. 7. The present study suggests that inhibition of gastric motor function by low doses of endotoxin involves activation of capsaicin-sensitive afferent neurones and neuronal NOS in the brainstem.

Animals↗