The effect of Escherichia coli endotoxin on plasma histaminase activity in the domestic fowl and the involvement of caeruloplasmin.

The injection of four-to nine-week-old fowls with Escherichia coli O111:B4 endotoxin (0-1 and 1-0 mg/kg) produced a two to eight fold rise in the histaminase activity of the plasma 24 h afterwards. In some cases this increase was still detectable after 48 h. This activity was strongly correlated with the p-phenylenediamine oxidase activity of caeruloplasmin. Electrophoretic studies with 7-5 per cent polyacrylamide gels indicated that fowl caeruloplasmin also was histaminase and putrescinase activity and that the release of this protein from the liver by endotoxin is largely responsible for the increase in the activity of the plasma. In untreated fowls this activity was lower than published values for several mammals and does not explain the relative resistance of the fowl to the acute effects of endotoxins and large doses of histamine.     

Characterization of release of tumor necrosis factor, interleukin-1, and superoxide anion from equine white blood cells in response to endotoxin

Direct effects of endotoxin (lipopolysaccharide [LPS]) on equine WBC are known to stimulate the release of a variety of mediators including thromboxane, prostacyclin, and leukotrienes. In this study, 0.1 microgram of LPS/ml stimulated an early increase in tumor necrosis factor, succeeded by an increase in interleukin-1, but concentrations of LPS up to 5.0 micrograms/ml caused no significant increase in superoxide anion release. The concentration of LPS (0.1 microgram/ml) used in this experiment was in the range of concentrations measured in plasma of some horses with gastrointestinal problems. These results indicate that mediators released in response to low concentrations of LPS may be responsible for many of the LPS-induced pathophysiologic effects. This is indicated because concentrations of LPS detected in plasma of some horses with severe gastrointestinal problems are approximately 0.1 microgram/ml, a concentration that will stimulate cells to produce tumor necrosis factor, but will not stimulate any other measurable cytotoxic effect.     

Pathologic changes and tissue gentamicin concentrations after intravenous gentamicin administration in clinically normal and endotoxemic cats

Hematologic and serum biochemical values, tissue gentamicin concentrations, and renal pathologic changes were determined in clinically normal and endotoxemic cats given 3 mg of gentamicin/kg of body weight, IV. Endotoxemia was induced by IV administration of 0.5 microgram of Escherichia coli endotoxin/kg of body weight. In experiment 1, 6 cats were given endotoxin. After rectal temperature increased at least 1 degree C, cats were given gentamicin. Blood samples were collected before and at 1 and 3 hours after administration of gentamicin. With the exception of severe leukopenia, other hematologic changes or changes in serum biochemical values were not observed. In experiment 2, 24 cats were allotted to 4 groups and were given gentamicin, endotoxin, gentamicin plus endotoxin, or neither substance. Three hours later, cats were euthanatized, and tissue and body fluid specimens were obtained and were assayed for gentamicin concentration. Kidney specimens were examined microscopically. Endotoxemic cats had more gentamicin in the renal medulla than did control cats, but none of the cats had detectable renal lesions. The possible nephrotoxic synergism between gentamicin and severe endotoxemia and the lack of major differences in gentamicin concentration in extrarenal tissues indicated that the dosage of gentamicin in endotoxemic cats does not have to exceed the dosage recommended for clinically normal cats. A single dose of gentamicin administered IV did not cause renal damage in mildly endotoxemic cats, but nephrotoxicity ascribed to multiple doses of gentamicin in more severely endotoxemic cats needs to be evaluated.     

Effect of Escherichia coli endotoxin on tissue lipoprotein lipase activities in chickens

1. Four-week-old broiler chickens were injected intravenously with from 0.01 to 1 mg of E. coli endotoxin/kg body weight or with saline. 2. At all doses used endotoxin markedly depressed food intake and lipoprotein lipase activities in muscle and adipose tissue within 8 h. Heart lipoprotein lipase activity was significantly depressed only at doses of 0.1 mg endotoxin/kg body weight or greater. 3. Treatment of birds with 0.3 mg endotoxin/kg body weight reduced post-heparin lipoprotein lipase activity to 0.13 of that in control birds in 8 h. 4. Endotoxin generally depressed plasma very-low-density lipoprotein concentration. Plasma non-esterified fatty acid concentration was significantly elevated only in birds given 1 mg endotoxin/kg body weight. 5. Fatty acid synthetase activity in the liver of endotoxin-treated birds was significantly lower than in control birds 16 h after administration of endoxin, but not after 8 h. 6. These results show that tissue lipoprotein lipase activity in birds is very responsive to E. coli endotoxin, as in mammals. Hypertriglyceridaemia occurs only occasionally in endotoxin-treated chickens, most probably because of the particularly close relationship between food intake and hepatic lipoprotein synthesis in birds.     

Preliminary safety and biological efficacy studies of ethyl pyruvate in normal mature horses

Reasons for performing the study: Endotoxaemia causes substantial morbidity and mortality in horses with colic and sepsis. Ethyl pyruvate is a novel anti‐inflammatory medication that improved survival in preclinical models of severe sepsis endotoxaemia and intestinal ischaemia and reperfusion in rodents, swine, sheep and dogs and may be a useful medication in horses. Hypothesis: Ethyl pyruvate has no adverse effects in normal horses and is biologically active based on suppression of proinflammatory gene expression in endotoxin stimulated whole blood, in vitro. Methods: Physical and neurological examinations, behaviour scores, electrocardiograms and clinicopathological tests were performed on 5 normal healthy horses receiving 4 different doses of ethyl pyruvate. Doses included 0, 50, 100 and 150 mg/kg bwt administered in a randomised crossover design with a 2 week washout period between doses. Biological efficacy was assessed by stimulating whole blood with endotoxin from the horses that received ethyl pyruvate prior to and 1 and 6 h after drug infusion. Gene expression for TNFα, IL‐1β and IL‐6 was assessed. Results: There were no effects of drug or dose (0, 50, 100 or 150 mg/kg bwt) on any of the physical or neurological examination, behaviour factors, electrocardiogram or clinical pathological results collected from any of the horses. All parameters measured remained within the normal reference range. There was a significant reduction in TNFα, IL‐1β and IL‐6 gene expression in endotoxin stimulated whole blood from horses 6 h after receiving 150 mg/kg bwt ethyl pyruvate. There were no detectable effects on gene expression of any of the other doses of ethyl pyruvate tested. Conclusion: We were unable to detect any detrimental effects of ethyl pyruvate administration in normal horses. Ethyl pyruvate significantly decreased proinflammatory gene expression in endotoxin stimulated blood 6 h after drug administration. Clinical relevance: Ethyl pyruvate may be a safe, effective medication in endotoxaemic horses.     

Effects of allopurinol on endotoxin-induced increase in serum xanthine oxidase in the horse

Using a modified bovine milk enzyme kinetic assay, xanthine oxidase activity of serum collected from 34 adult, healthy horses of both sexes was determined. Enzyme activity varied from 0 to 126 mU litre-1 with a mean of 44.95 +/- 21.05 mU litre-1. The optimal pH and temperature for maximal activity were 7.8 and 28 degrees C, respectively. Freezing the serum for four days at -70 degrees C did not destroy the enzyme activity. Various doses (25, 50 and 75 micrograms kg-1, intraperitoneally) of endotoxin (lipopolysaccharide D1 Escherichia coli O26:B6) previously known to have caused moderate to severe systemic clinical signs of endotoxaemia in horses produced a significant dose related increase in serum xanthine oxidase activity. Pretreatment (12 hours) with allopurinol (5 and 50 mg kg-1, intravenously [corrected]) significantly reduced the rise in xanthine oxidase activity in endotoxin (50 micrograms kg-1, intraperitoneally) treated horses. The results of this study suggest that xanthine oxidase catalysed production of superoxide radicals may play a role in the pathogenesis of endotoxaemia and that allopurinol, an alternate substrate, should be further evaluated for its therapeutic potential in endotoxin related systemic diseases in horses.     

Vaccination of cows with rough Escherichia coli mutants fails to protect against experimental intramammary bacterial challenge

Vaccination of cows with rough Escherichia coli mutants fails to protect against experimental intramammary bacterial challenge. Vaccine A, a heat-killed Re mutant of strain K12, (UB 1574), was administered as a single parenteral and local dose to 5 cows with 3 control animals and Vaccine B, a heat-killed mutant of O111:B4 (J5) was administered as three parenteral doses into 5 cows with 5 control animals. Following intramammary challenge with a smooth wild-type strain (P4), an acute, severe clinical mastitis developed in all 14 quarters (9 vaccine A and 5 vaccine B) of the vaccinated animals which was indistinguishable from that in the 11 quarters of the control animals. Following vaccine B there was an elevation in serum IgG1 and IgG2 antibody to the common core antigen of endotoxin which, in contrast to the control animals, showed a further increase after intramammary infection.     

Effects of Pasteurella multocida endotoxins on turkey poults

Studies of turkey poult responses to Pasteurella multocida endotoxins indicated that lipopolysaccharide (LPS) preparations from two highly pathogenic strains and free endotoxin from one of these strains were all similar in lethal toxicity. Lethal intravenous doses were generally high, 1 mg or more for 1-week-old poults (13.3 mg/kg). The toxic effects of LPS were not increased by repeated administration of small hourly doses. For both forms of endotoxin, the relationship between dose and response was considered erratic. Attempts to increase the susceptibility of poults to LPS by administering a liver-damaging substance (galactosamine) or a histamine-releasing substance (compound 48/80) or by performing surgical bursectomy were not effective. The LPS did not provoke a dermal Shwartzman reaction, even though doses used were 10 times those that produced a characteristic reaction in a rabbit.     

Antagonism of endotoxin-induced disruption of equine gastrointestinal motility with the platelet-activating factor antagonist WEB 2086

The effect of pre-treatment with a selective platelet-activating factor (PAF) antagonist, WEB 2086, on the actions of low-dose endotoxin was evaluated in ponies prepared with gastrointestinal strain gauges. Endotoxin (0.1 microgram/kg i.v.) produced a marked reduction in gastric contraction amplitude and rate, and an increased frequency and reduced duration of jejunal phase III activity fronts (AFs). WEB 2086 (6.6 mg/kg) administered i.v. 10 min before the endotoxin, produced significant antagonism (P less than 0.001) of the effect of endotoxin on gastric contraction amplitude and rate. The combination of WEB 2086 and endotoxin produced gastric contractions of significantly (P less than 0.01) higher frequency than in the control studies. WEB 2086 also reduced endotoxin-induced abnormal phase III AFs in the jejunum and increases in heart rate and packed cell volume. These results provide evidence that endogenous PAF plays a role in mediating the acute effects of endotoxin on equine gastrointestinal motility.     

Respiratory, renal, hematologic, and serum biochemical effects of hypertonic saline solution in endotoxemic calves

The respiratory, renal, hematologic, and serum biochemical effects of hypertonic saline solution (HSS) treatment were examined in 12 endotoxic, pentobarbital-anesthetized calves (8 to 20 days old). Escherichia coli endotoxin (055:B5) was infused IV at a rate of 0.1 microgram/kg of body weight over 30 minutes. Endotoxin induced severe respiratory effects, with marked hypoxemia and increases in arterial-alveolar O2 gradient (P[A-a]O2), physiologic shunt fraction (Qs/Qt), and physiologic dead space to tidal volume ratio (Vd/Vt). Oxygen consumption was decreased, despite an increase in the systemic O2 extraction ratio. Peak effects were observed at the end of endotoxin infusion. The renal response to endotoxemia was characterized by a decrease in free-water reabsorption and osmotic clearance, as well as a decrease in sodium and phosphorus excretion. Endotoxemia induced leukopenia, thrombocytopenia, hyperphosphatemia, hypoglycemia, acidemia, and increased serum alkaline phosphatase concentrations. Calves were treated with HSS (2,400 mosm/L of NaCl, 4 ml/kg, n = 4) or an equivalent sodium load of isotonic saline solution (ISS; 300 mosm/L of NaCl, 32 ml/kg, n = 4 90 minutes after the end of endotoxin administration. Both solutions were infused over a 4- to 6-minute period. A control group (n = 4) was not treated. Infusion of HSS or ISS failed to induce a significant change in Pao2, P(A-a)O2, (Qs/Qt), (Vd/Vt), or oxygen consumption. Both solutions increased systemic oxygen delivery to above pre-endotoxin values. Hypertonic saline infusion induced significant (P less than 0.05) increases in serum Na and Cl concentrations and osmolality, whereas ISS induced a significant increase in serum Cl concentration and a significant decrease in serum phosphorus concentration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Endotoxin-induced changes in the hemostatic system in neonatal calves: the effect of antiserum to a mutant Escherichia coli (J-5)

Changes in the hemostatic system were studied in 22 neonatal calves given a small dosage of Escherichia coli endotoxin (0.5 microgram/kg) by slow (5-hour) IV infusion. The effect of pretreatment with an antiserum to mutant of E coli O111:B4 (J-5) was evaluated. The platelet count, plasma fibrinogen concentration, prothrombin time, and activated partial thromboplastin time changed significantly from base line during and after endotoxin infusions in all calves. The mean platelet count was significantly decreased from 1 through 24 hours after endotoxin infusion was started. Mean plasma fibrinogen was decreased 2 through 12 hours after endotoxin infusion was started. The mean prothrombin time and activated partial thromboplastin time were significantly greater than base line at 3 to 6 hours and 3 to 12 hours, respectively, after endotoxin infusion was started. Serum concentration of fibrinolytic degradation products remained less than 10 micrograms/ml. Bovine J-5 antiserum did not prevent the endotoxin-induced changes in the hemostatic system of these neonatal calves.     

Endotoxemia in neonatal calves given antiserum to a mutant Escherichia coli (J-5)

Endotoxemia was characterized in neonatal calves given a small amount of colostrum and smooth Escherichia coli endotoxin by small-dosage (0.5 microgram/kg of body weight), slow (5-hour) IV infusion to mimic natural conditions. Responses were compared among 22 calves freely allotted to groups treated with saline solution (group I), preimmunization plasma (PP, group II), or antiserum to the rough mutant of E coli O111:B4 (J-5, group III) before endotoxin was infused. Bovine J-5 antiserum was produced by immunization of 4 cattle with J-5 boiled cell bacterin. The antiserum titers of immunoglobulin (Ig) M, IgG1, and IgG2 to the J-5 boiled cells, as determined by enzyme-linked immunosorbent assay, were 240, 7,680, and 960, respectively. The PP had enzyme-linked immunosorbent assay titers to J-5 of 240, 480, and 60 of IgM, IgG1, and IgG2, respectively. Endotoxemia in the 3 groups was characterized by significant (P less than 0.05) time-related changes in rectal temperature, heart rate, respiratory rate, capillary refill time, oral mucous membranes, nose moistness, scleral injection, attitude, PCV, total plasma protein concentration, WBC count and differential, plasma glucose, and lactate concentrations. The only significant treatment effects on clinical or laboratory values were higher mean total plasma protein concentrations in groups II and III 10 to 30 hours after endotoxin infusion was started than that in group I and increasing mean most-severe attitude abnormality score in groups I, III, and II (P less than 0.05). The administration of bovine J-5 antiserum to neonatal calves resulted in significantly higher serum IgG1 and IgG2 titers to J-5 boiled cells (P less than 0.05), and cross-reactive IgG2 to the challenge endotoxin (P less than 0.01) than did treatment with PP or saline solution; however, this antiserum did not mitigate the effects of sublethal endotoxemia. There was a significant negative correlation between IgG2 to J-5 at base line and the mean attitude abnormality score at 4.5 hours after infusion was started (P less than 0.05).     

Synergistic action of E. coli endotoxin and Pasteurella multocida type A for the induction of bronchopneumonia in pigs

This study aimed to investigate whether Escherichia coli endotoxin (LPS) may predispose the lung to an infection with Pasteurella multocida type A (Pma) and to determine the LPS concentration needed to reproduce clinical signs of bronchopneumonia. Twenty-four hours before inoculating Pma or sterile growth medium, piglets were tracheally instilled with 10, 100 or 400 microg/kg LPS. Cough, body temperature, daily weight gain (DWG) bronchoalveolar lavage fluid (BALF) cells and volume of pneumonic lung were measured. Changes in breathing pattern (Penh) were assessed by whole body barometric plethysmography. No significant changes were observed in Pma-treated or in control animals. Each LPS doses induced DWG reduction while the higher generated a severe subacute interstitial pneumonia causing hyperthermia and an increase in Penh. The combination of the lower LPS doses with Pma produced an asymptomatic bronchopneumonia leading to DWG reduction, rise in Penh and an increase in BALF macrophages and neutrophils. With 400 microg/kg LPS, Pma worsened the inflammatory process as illustrated by cough, hyperthermia, major DWG reduction and by a greater Penh response. Lung lesions consisted of severe exudative bronchopneumonia. We concluded that LPS may negatively influence growth, predispose to persisting lung inflammatory process and promote Pma infection depending on the dose previously administered.     

Haemodynamic, pathological, haematological and behavioural changes during endotoxin infusion in equine neonates

The purpose of this study was to evaluate the effects of experimentally induced sublethal endotoxaemia in equine neonates. Four foals, between two and five days of age, were infused intravenously with 0.5 microgram/kg bodyweight of Salmonella typhimurium endotoxin (LPS) over a 5 h period. A four-day-old and a five-day-old foal, similarly infused with sterile isotonic saline, served as controls. Clinical signs were monitored, blood samples obtained for evaluation of selected haematological and biochemical parameters; and haemodynamic parameters were recorded hourly during the infusion, as well as 6 and 24 h post infusion. Depression, anorexia, increased rectal temperature, leucopenia followed by leucocytosis, hypoglycaemia, increased prothrombin time, partial thromboplastin time (APTT), pulmonary artery pressure, pulmonary artery wedge pressure, right atrial pressure, pulmonary and systemic vascular resistance and mild hypoxaemia were consistent findings in the foals receiving endotoxin. There was marked variation over time in the above parameters, during the infusion. Shock was not induced, and the foals appeared to be healthy shortly after the infusion was discontinued. The return to baseline values of body temperature (3 of 4 foals), APTT (1 of 4 foals) and neutrophil count (2 of 4 foals), during endotoxin infusion, suggests induction of early tolerance. The control foals remained alert and the temperature, prothrombin time and fibrinogen remained stable during the study. Hyperglycaemia, transient increased APTT and variations in selected haemodynamic parameters were recorded in the control foals during the infusion.     

Equine Escherichia coli endotoxemia: comparison of intravenous and intraperitoneal endotoxin administration.

Certain physiologic and hematologic data were determined in ponies given Escherichia coli endotoxin by three routes: single IV dose, single intraperitoneal (IP) dose, and multiple IP boluses. In all ponies, the reaction was characterized by weakness, depression, peripheral circulatory abnormalities, and pyrexia. The pyrexia was more severe and was sustained in the ponies given multiple IP bolus endotoxin. Changes in packed cell volume, peripheral blood neutrophil, lymphocyte, and thrombocyte counts, and blood glucose were noticed in the three groups. Blood lactate and beta-glucuronidase values were determined and increases occurred only in the two IP endotoxin administration groups. A fibrinogen increase was observed in only the multiple IP bolus group. Attempts were made to correlate the lactate and beta-glucuronidase values with the severity and prognosis of the endotoxemia response. In general, the single IV bolus and, to a lesser extent, the single IP bolus endotoxin produced abrupt but transient responses. The multiple IP bolus endotoxin administration produced a more gradual and sustained response, which was more closely comparable with a clinical gastrointestinal disease problem than the other routes of administration produced.     

Host response to Pasteurella multocida turbinate atrophy toxin in swine.

A porcine strain of Pasteurella multocida (serotype D:3) produced a toxin causing turbinate atrophy (TA) in pigs. The toxin (TAT), processed on a high performance liquid chromatography size exclusion column, eluted as a single peak (molecular weight of about 160,000) containing trace amounts of endotoxin (lipopolysaccharide, LPS; protein:LPS, 85:1). The eluted fraction migrated on sodium dodecyl sulfate polyacrylamide gels as a single band. It could be prevented from dissociating into two prominent polypeptides by addition of a protease inhibitor. A single dose (2.0 to 79.0 micrograms/kg) of TAT given to pigs intravenously was lethal. Doses from 0.02 to 1.0 microgram/kg caused transient clinical signs of porcine systemic toxicosis with reduced appetite, generalized weakness, depression, lethargy, weight loss, and in some instances, death. Intradermal doses of TAT (greater than or equal to 0.1 microgram/site) produced hemorrhagic areas within four hours. Systemically, TAT causes bilateral TA, lymphopenia, liver dysfunctions, and possible renal impairment. Affinity of TAT for cells of epithelial origin was demonstrated in mice given 125I-TAT. In vitro, TAT stimulated DNA and protein syntheses of peripheral blood lymphocytes and suppressed syntheses in turbinate and kidney cell cultures without being cytolytic. Biological effects of TAT were eliminated by exposure to either heat, trypsin or anti-TAT antibody.     

Hemodynamic response of endotoxemic calves to treatment with small-volume hypertonic saline solution

The hemodynamic effects of hypertonic saline solution (HSS) resuscitation on endotoxic shock were examined in pentobarbital-anesthetized calves (8 to 20 days old). Escherichia coli (055:B5) endotoxin was infused IV at dosage of 0.1 microgram/kg of body weight for 30 minutes. Endotoxin induced large decreases in cardiac index, stroke volume, maximal rate of change of left ventricular pressure (+dP/dtmax), femoral and mesenteric arterial blood flow, glomerular filtration rate, urine production, and mean aortic pressure. Severe pulmonary arterial hypertension and increased pulmonary vascular resistance were evident at the end of endotoxin infusion. Treatment with HSS (2,400 mosm of NaCl/L, 4 ml/kg) or an equivalent sodium load of isotonic saline solution (ISS: 300 mosm of NaCl/L, 32 ml/kg) was administered 90 minutes after the end of endotoxin administration. Both solutions were infused IV over a 4- to 6-minute period. Administration of HSS induced immediate and significant (P less than 0.05) increase in stroke volume and central venous pressure, as well as significant decrease in pulmonary vascular resistance. These effects were sustained for 60 minutes, after which all variables returned toward preinfusion values. The hemodynamic response to HSS administration was suggestive of rapid plasma volume expansion and redistribution of cardiac output toward splanchnic circulation. Plasma volume expansion by HSS was minimal 60 minutes after resuscitation. Administration of ISS induced significant increase in cardiac index, stroke volume, femoral arterial blood flow, and urine production. These effects were sustained for 120 minutes, at which time, calves were euthanatized. Compared with HSS, ISS induced sustained increase in mean pulmonary arterial pressure and only a small increase in mesenteric arterial blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)     

Endotoxin-induced fever and associated haematological and blood biochemical changes in the goat: the effect of repeated administration and the influence of flurbiprofen

Flurbiprofen, a potent non-steroidal anti-inflammatory and antipyretic agent, was given as an intravenous infusion (2 mg/kg) followed by a bolus injection of 1 mg/kg six hours later. After drug administration body temperature and rumen contractions were slightly depressed, whereas urea values gradually increased; serum sorbitol dehydrogenase (SDH) activity, plasma iron concentration and the number of circulating lymphocytes were significantly lower. Intravenous injection of endotoxin from Escherichia coli O111B4 (0.1 microgram/kg) caused shivering, fever, inhibition of rumen contractions, changes in heart rate, lymphopenia, neutropenia followed by neutrophylic leucocytosis, changes in urea values, hypoferraemia, hypozincaemia and a decline in serum alkaline phosphatase (ALP) activity, whereas gamma-glutamyltranspeptidase, glutamic oxalacetic transaminase, lactic dehydrogenase and SDH values were not significantly altered. Pretreatment with flurbiprofen completely abolished the febrile reactions to endotoxin. The endotoxin-induced inhibition of rumen contractions was only delayed. The drug blocked the initial tachycardia to endotoxin but did not prevent the secondary biphasic increase in heart rate. Flurbiprofen failed to modify the endotoxin-induced decrease in both plasma zinc and serum ALP activity whereas the decline in plasma iron concentration was delayed. After drug pretreatment the changes in circulating white blood cells were more pronounced. These data demonstrate that most of the haematological, blood biochemical and clinical effects of endotoxin cannot be blocked by flurbiprofen, and that these effects are not due to the increase in body temperature alone. Tolerance induced by repetitive daily intravenous administration of endotoxin resulted in an almost complete abolition of all the effects. However, the plasma iron values from tolerant goats were significantly lower than those from non-tolerant animals, which demonstrates that the development of a refractory state can result in modification of this biochemical parameter.     

The effect of Escherichia coli endotoxins on the concentrations of corticosterone and growth hormone in the plasma of the domestic fowl

The intravenous injection of chickens aged six to 11 weeks with Escherichia coli endotoxins (serogroups O111 and O78) produced a large increase in the plasma corticosterone concentration which was maximal (five to 10-fold) after 1 h and still evident after 8 h. It did not vary with the dose over the range 0.1 to 2 mg/kg and was smaller than that produced by adrenocorticotrophic hormone (ACTH) (20 iu/kg). A decrease in growth hormone concentration was detected between 1 and 2 h after endotoxin administration in six- to seven-week-old birds, this change being opposite to that which occurs in man.     

Kinetics, dose response, tachyphylaxis and cross-tachyphylaxis of vascular leakage induced by endotoxin, zymosan-activated plasma and platelet-activating factor in the horse

Vascular leakage induced by intradermal injection of endotoxin, zymosan-activated plasma (ZAP) and platelet-activating factor (PAF) was measured in nine Thoroughbreds using 125-iodine human serum albumin (¹²⁵I-HSA) as a marker in the blood. ZAP and PAF produced dose-dependent increases in vascular permeability with the maximum occurring within the first 15 min after injection. The vascular leakage induced by endotoxin was also dose-dependent, but the maximum occurred 2 h after intradermal injection. Intradermal sites previously injected with endotoxin were refractory to a second injection of endotoxin for up to 5 days. However, sites injected with endotoxin and re-injected with either ZAP or PAF remained responsive with increased vascular leakage compared to saline injected control sites re-injected with either ZAP or PAF. Diminished response to endotoxin challenge may contribute to the poor prognosis of endotoxaemia in the horse.