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PubMed1988

Burst-patterned stimulation promotes nicotinic transmission in isolated perfused rat sympathetic ganglia.

1. Intracellular recordings of small nicotinic excitatory postsynaptic potentials (EPSPs) were made from rostral cells in superior cervical ganglia (SCG) of rats during and after test stimulation of small preganglionic fibre bundles, while perfusing the isolated ganglia via their arterial vasculature. Perfusion, in contrast to superfusion of desheathed ganglia, (a) produced much more rapid and complete equilibration of drugs and ions at synaptic sites, (b) greatly reduced depression of EPSPs during high-frequency stimulation, and (c) largely prevented slowing of conduction, presumably by minimizing accumulation of K+ in the intercellular spaces surrounding these sites. 2. Preganglionic inputs were found to fall into two major groups: those in which the EPSP amplitude during 200 pulse trains was facilitated and others in which it was depressed as stimulation frequency in the train was increased from 2 to 20 Hz or from 0.2 to 1.25 Hz. Both the facilitation and the depression were presynaptic, since they occurred without changes in miniature EPSP amplitude. 3. The maximum maintained facilitation was reached at 5-10 Hz with a value 1.26 times the 1.0 Hz control. This was associated with an increase in the binomial parameter n. While long 20 Hz trains produced a similar facilitation to an early plateau, and an increase in n, EPSP amplitude declined as the train progressed. This was associated with a decrease in the binomial parameter p. 4. Unlike the 20 Hz trains, stimulation with 0.5 s long, 20 Hz bursts given every 8 s produced a marked potentiation in facilitating units and this was maintained for as long as the stimulation was continued (3-11 min). Burst-patterned potentiation was 1.66 times larger than the facilitation evoked by tonic stimulation at the same average frequency (1.25 Hz), and more than twice that achieved with long, 200 pulse trains. The potentiation was associated with increases in both n and p in the first EPSP of the burst and mainly with an increase in n at the end of the burst. Potentiation persisted unchanged for about 30 s following the return to control 0.2 Hz stimulation, before declining to control levels over the next 2-3 min. Depressing units on average showed neither burst-patterned potentiation nor post-burst-patterned potentiation. 5. All inputs tested in Locke solution in which Ca2+ was reduced to 0.5 mM with addition of 1.2 mM-Mn2+ or 3.8 mM-MgCl2 exhibited a pronounced facilitation within each burst but no extension of potentiation into ensuing bursts. Both burst-patterned potentiation and the post-burst-patterned potentiation were abolished.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1980

Application of the isolated perfused rat kidney in nephrology.

Three approaches, each adapted for a specific type of investigation, have been developed for perfusion of isolated rat kidneys. Single-pass perfusion is preferred for physiological or pathophysiological work since the effect of metabolic substrates on sodium transport can be evaluated without the possible curtailing effect of catabolic substrates which can arise when perfusate is recirculated. Recirculation is preferred for biochemical studies since metabolic effects accumulate in time when this approach is employed. The kidney's role in the degradation and framentation of peptide hormones can thus be analyzed. The third approach, recirculation with dialysis, incorporates the advantages of the first two approaches; expensive colloids such as albumin can be used, and the contancy of functional parameters of single-pass perfusion may be achieved.

Animals↗
PubMed1988

Halothane decreases albumin and transferrin synthesis: studies in the isolated, perfused rat liver and in the intact rat.

Isolated perfused rat livers exposed to 1.5% halothane (equivalent to 1.35 MAC) in O2/CO2 or to O2/CO2 alone produced urea, as well as albumin and transferrin (both measured by immunodiffusion), at constant rates during a 4.25-h perfusion. Urea production did not differ in the two treatment groups, but halothane depressed albumin and transferrin synthesis 43% and 45%, respectively. Intact rats were also exposed to halothane, after which albumin synthesis was measured by the (14C)carbonate technique. The minimum halothane concentration required to insure sufficient relaxation for ventilation was selected and ranged from 1.0 to 1.5%. Measurements were made in control rats not exposed to halothane (group I) and in halothane exposed rats immediately after 1 h of anesthesia (group II), 24 h after the start of 1 h of anesthesia (group III), and immediately after 1/2 h of anesthesia preceded by a 1-h exposure 24 h earlier (group IV). Single exposures to halothane (groups II and III) resulted in a decrease in albumin synthesis immediately or 24 h later that did not differ significantly from controls (group I). However, halothane given twice to rats at 24-h intervals (group IV) reduced their mean albumin synthesis rate to half that of controls. The early onset and constancy of halothane depression of export protein synthesis by isolated, perfused livers may reflect a response to halothane itself, rather than an effect resulting from the accumulation of halothane metabolites. Similarly, reduction of albumin synthesis in intact rats immediately after a second halothane exposure may indicate a response to halothane, rather than to halothane metabolites.

Albumins↗
PubMed1983

Influence of bradykinin on glucose uptake and metabolism studied in isolated cardiac myocytes and isolated perfused rat hearts.

To study whether bradykinin influences myocardial glucose metabolism as suggested for skeletal muscle, we studied the effect of bradykinin on myocardial glucose transport using isolated cardiac cells and on glucose metabolism using the isolated perfused rat heart. In isolated cardiac myocytes bradykinin alone had no influence on the initial velocity of basal glucose transport nor on the sensitivity of the glucose carrier towards stimulation by insulin. By contrast, in isolated perfused hearts bradykinin increased the rate of glucose uptake and oxidation as well as the formation of lactate independently of the action of insulin. In diabetic hearts, neither bradykinin nor insulin alone had a significant influence on myocardial glucose oxidation, however, both hormones together act synergistically to improve glucose oxidation. These data suggest that bradykinin enhanced the nutritional flow across the capillary wall and, thereby, indirectly accelerates the glucose metabolism in the isolated perfused heart. There is no evidence for a direct effect of bradykinin on the rate of glucose transport in the heart.

Animals↗
PubMed1987

Isolation perfusion with cisplatin for malignant melanoma of the limbs.

The role of hyperthermic isolation perfusion in the treatment of advanced melanoma of the limbs is clearly important. However, attention has in the past been focussed mainly on surgical aspects of the procedure. Whereas, equivalent interest in chemotherapy considerations has been lacking. A group of 15 patients have been treated by hyperthermic isolated perfusion for advanced melanoma of the limbs. The chemotherapeutic agent used was cisplatin. The follow-up period was 6 to 60 months. None of these patients had any sign or symptoms of toxicity from the drug. Twelve of these 15 patients are free of disease currently. There was one case of mortality due to unrelated cause and two cases of mortality due to disseminated disease which developed 6 months and 30 months, respectively, posttreatment. Since not uncommon toxic side effects from other drugs used for this procedure is significant, these results suggest that cisplatin may be used as an alternative chemotherapeutic agent in isolation perfusion for advanced melanoma of the extremities.

Aged↗
PubMed1989

Hemodynamic and metabolic responses to leukotriene C4 in isolated perfused rat liver.

Responses of isolated perfused rat liver to leukotriene C4 were studied in order to assess the mechanisms involved in leukotriene-mediated liver injury. Infusion of leukotriene C4 (11 and 44 pmoles per min per gm liver weight) into the portal vein resulted in a rise in portal pressure, a decrease in oxygen consumption, an increase in hepatic glucose and lactate efflux and lactate/pyruvate ratio in the perfusate and a small decrease in bile flow. Isoproterenol (1 microM) counteracted the effects of leukotriene C4 on respiration and portal pressure, whereas bile flow and glucose efflux were reversibly stimulated. The same changes were observed upon withdrawal of leukotriene C4. The release of glucose was correlated with the increase in oxygen consumption upon both isoproterenol addition and withdrawal of leukotriene C4. These results are indicative of leukotriene C4-induced microcirculatory redistribution of perfusate flow. Since, in the presence of nitroprusside (50 microM), both the effects of leukotriene C4 and their reversal by isoproterenol were diminished, a vascular site of action can be assumed. Accordingly, the accompanying metabolic responses can be explained by gradual changes in oxygen supply to parts of the liver. Reversibility of the leukotriene C4 effects and lack of short-term impairment of viability of the isolated liver suggest that leukotriene-mediated liver injury is a long-term effect related to events subsequent to microcirculatory changes.

Animals↗
PubMed2005

Gene therapy in in vivo isolated perfusion models.

Locoregional administration of a genetic construct by means of in vivo, in situ isolated perfusion (IP) of a target organ or extremity is a method that may increase in vivo efficacy. Vascular isolation and perfusion minimizes systemic exposure and thereby reduces unwanted side effects. Isolated hepatic perfusion (IHP) is the most extensively studied IP model, especially in gene therapy protocols for inborn errors of metabolism. To achieve stable transduction most frequently retroviruses are used in IHP. IHP is combined with hepatectomy or vascular ligation of liver lobes to induce liver regeneration increasing transduction efficacy. When adenoviruses are used in IHP high transduction percentages of hepatocytes can be achieved without significant toxicity. In tumor models adenoviral IHP has been performed, but has not been very successful up till now. Isolated limb perfusion (ILP) is a promising treatment modality in pre-clinical cancer gene therapy studies. After ILP a homogeneous distribution of transduced cells was demonstrated especially at the viable rim of the tumor and around tumor associated vessels. Moreover complete tumor responses have been observed. Isolated pulmonary perfusion (IPP) results in selective expression in the perfused lung and the duration of expression is longer than after systemic administration. In rats a significant decrease of tumor nodules upon IPP can be achieved. Furthermore other less studied perfusion models are discussed: isolated kidney perfusion (IKP), isolated spleen perfusion (ISP) and isolated cardiac perfusion (ICP). IP is a methodology that delivers vectors highly selectively, with a long exposure time and high concentrations at the target side. This results in higher transduction rates and thereby may improve therapeutic effects.

Animals↗
PubMed1987

Early intraneuronal mobilization and deamination of noradrenaline during global ischemia in the isolated perfused rat heart.

Isolated rat hearts were perfused according to the Langendorff technique and both extraneuronal uptake of noradrenaline and COMT were inhibited. The noradrenergic neurones were first prelabelled with 3H-(-)-noradrenaline (13 nmol/l). Thereafter the hearts were submitted to global ischemia (perfusion rate reduced from 5 up to 0.5 ml/min) for 60 min and subsequently reperfused for 5 min. The coronary effluent was continuously collected and analyzed for the appearance of 3H-noradrenaline and its metabolites. 1. Global ischemia was associated with an early release of 3H-noradrenaline. At reperfusion a brisk increase in the FRL of 3H-noradrenaline was observed which may indicate that, on severe restriction in coronary flow, perfusion of the tissue became heterogenous and thus partially masked the amount of 3H-noradrenaline released from the noradrenergic nerve terminals. Gradual reduction in coronary flow also progressively reduced (but did not abolish) the total formation of 3H-DOPEG. 2. The maximal efflux of 3H-noradrenaline was observed during the 1st min of reperfusion whereafter the efflux declined rapidly, indicating a wash-out of transmitter trapped in the extracellular space. The efflux of the lipophilic metabolite 3H-DOPEG, on the other hand, continuously increased during the reperfusion. This was due to both new formation and "wash-out" of 3H-DOPEG retained and/or distributed into the tissue during the period of restricted flow. 3. Neither a reduction of the extracellular calcium concentration (from 2.6 mmol/l to 0.1 mmol/l) nor the presence of the calcium entry blocker verapamil (250 nmol/l) reduced the efflux of 3H-noradrenaline seen during ischemia and reperfusion. 4. Desipramine (100 nmol/l) markedly reduced the ischemia-induced release of 3H-noradrenaline and simultaneously attenuated the formation of 3H-DOPEG. 5. A moderate reduction in the ischemia-induced mobilization of 3H-noradrenaline was seen in hearts perfused with 1 mumol/l reserpine, whereas the formation of 3H-DOPEG from such hearts was markedly higher than in corresponding controls. Only minor deviations from this pattern was observed when desipramine was present in addition to reserpine. It is concluded that a severe restriction in myocardial perfusion rate is associated with an enhanced net leakage of vesicular noradrenaline. This results in a rise of the free axoplasmic noradrenaline concentration which, in combination with an altered transmembrane sodium gradient, induces an increased local release of noradrenaline partly mediated by a calcium-independent, carrier-mediated outward transport.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1996

Characterization of vascular P2 purinoceptors in the rat isolated perfused kidney.

In isolated, constant-pressure perfused rat kidneys at basal vascular tone, injected P2 purinoceptor agonists evoked vasoconstriction (alpha, beta-methylene ATP > beta, gamma-methylene ATP > ATP-gamma-S > 2-methylthio ATP > ATP > ADP = UTP). In kidneys with raised tone, the nucleotides produced vasodilatation at low doses (2-methylthio ATP > ADP = ATP = ATP-gamma-S > UTP; alpha, beta-methylene ATP and beta, gamma-methylene ATP, inactive), and constriction at high doses (alpha, beta-methylene ATP > beta, gamma-methylene ATP > ATP-gamma-S > 2-methylthio ATP > ADP = ATP > UTP). Removal of the endothelium abolished the dilator responses to the agonists. NG-Nitro-L-arginine methylester (L-NAME, 5 x 10(-5) M) abolished vasorelaxation in response to 2-methylthio ATP, a response which could be restored by additional L-arginine (3 x 10(-3) M). Both vasodilatation and constriction due to the nucleotides remained unaffected by indomethacin (3 x 10(-6) M), S-(p-nitrobenzyl)-6-thioinosine (3 x 10(-5) M) and 8-phenyltheophylline (3 x 10(-6) M). Pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 1-3 x 10(-6) M), inhibited vasoconstriction caused by alpha, beta-methylene ATP, 2-methylthio ATP and UTP, but not by ATP. Suramin (3 x 10(-5) M) caused a rightward shift of the dose-response curves for constriction caused by alpha, beta-methylene ATP (27-fold) and 2-methylthio ATP (5-fold), whereas the ATP curve was shifted to the left (20-fold). With Evans blue (10(-5) M), vasodilatation due to the nucleotides was abolished and the dose-response curves for vasoconstriction caused by ATP and UTP were shifted left more than 100-fold, the effect to both could not be antagonized by PPADS (3 x 10(-6) M). These results suggest: (1) the different rank orders of P2 purinoceptor agonist potencies for constrictor and dilator responses in perfused rat kidney are consistent with mediation via P2x and P2Y purinoceptors, respectively; (2) P2X purinoceptors, selectively sensitive to blockade by PPADS, are located on vascular smooth muscle; (3) endothelial P2Y purinoceptor stimulation results in vasodilatation involving NO synthesis but not release of prostanoids; (4) Evans blue, which appears to combine selective P2Y purinoceptor blockade and strong inhibition of ecto-nucleotidases, potentiates vasoconstriction in response to the degradable nucleotides, ATP, 2-methylthio ATP and UTP; (5) additionally, Evans blue unmasks a PPADS-insensitive P2U purinoceptor where the nearly equipotent nucleotides, ATP and UTP, can produce vasoconstriction.

Adenosine Triphosphate↗
PubMed1986

Identification of glucuronide metabolites of T-2 toxin and diacetoxyscirpenol in the bile of isolated perfused rat liver.

Isolated rat livers were perfused with either 2 mg T-2 toxin or diacetoxyscirpenol (DAS) in a recirculating perfusion system. To identify glucuronide conjugates, equal amounts of bile samples were incubated with and without (control) a beta-glucuronidase preparation and analyzed by capillary gas liquid chromatography-chemical ionization mass spectrometry. Enzyme treatment of bile obtained from liver perfused with T-2 toxin resulted in the detection of a total of 954 micrograms HT-2 toxin (control 6 micrograms), demonstrating that excretion into the bile was mainly as glucuronide conjugates. Minor metabolites of T-2 toxin in bile were identified as 3'-hydroxy HT-2 toxin (TC-3), 3'-hydroxy-7-hydroxy HT-2 toxin (TC-6), and the glucuronide form of T-2 triol (trace amount). The glucuronide conjugates of monoacetoxyscirpenol (340 micrograms) and scirpenetriol (10 micrograms) were found in bile obtained from liver perfused with DAS, while nonconjugated metabolites were not detected. It is assumed that considerable amounts of T-2 toxin and DAS were metabolized biphasically. In phase I both trichothecenes were deacetylated, in phase II the metabolites were conjugated giving rise to the glucuronic acid adducts.

Animals↗
PubMed1985

Age dependent phagocytosis of red cell membranes by the reticulohistiocytary system of the isolated perfused rat liver.

Isolated rat livers were perfused with a medium free of immune globulins, protein and hemoglobin to investigate age-dependent differences in the phagocytosis of erythrocyte membranes. Membranes of young erythrocytes were phagocyted significantly more than those of old ones. The control parameters of the liver function also were significantly higher during the increased phagocytosis of the young cells than for the old cells and the control group. In the aged animals the characteristic of the elimination curve is changing. The old livers eliminated less ghosts than the young ones. These results are significant.

Aging↗
PubMed1975

Phosphatidylglycerol in rat lung. I. Identification as a metabolically active phospholipid in isolated perfused rat lung.

Isolated rat lungs when perfused for 2 hr with [U-14]glucose, [2-14C]lactate, or [u-14]acetate, were found to contain a phos pholipid which represented a small percentage of the total phospholipid (3.9 per cent), and possessed the highest specific activity of any phospholipid. Using chromatographic, chemical, and mass spectral analysis, the phospholipid has been identified as phosphatidylglyercol. When [2-14C]lactate was present in the perfusion medium, 15.3 per cent of the lactate incorporated into phospholipids was incorporated into phosphatidylglyerol with a relative specific activity of 5.1 compared to phosphatidylcholine, 1.0, and phosphatidylethanolamine, 0.5. Phosphatidylglycerol also had the highest specific activity when lungs were perfused with [1-14C]acetate and [U-14]glucose. While the significance of the content and apparent metabolic activity of phosphatidylglycerol are unknown, its possible role in stabilizing the surfactant complex of lung is discussed.

Acetates↗
PubMed1991

Effect of V2 antagonist on clearance of arginine vasopressin by isolated perfused rat kidneys.

Isolated rat kidneys were perfused with Krebs-Henseleit-bovine serum albumin solution at a mean pressure of 99 +/- 2.6 mmHg. After control periods, arginine vasopressin (AVP) was added to the perfusate at a final calculated concentration of 25 pg/ml (2.5 x 10(-11) M). Urine and perfusate samples were collected at 15-min intervals for the following 60 min to measure kidney function and the renal clearance of immunoreactive AVP (irAVP). At 15-30 min after the addition of AVP, total renal clearance of irAVP was 1,623 +/- 190 microliters.min-1.g kidney wt-1. Glomerular filtration accounted for 35 +/- 3.0% of the total clearance, and 65 +/- 10.3% was cleared by peritubular pathways. Of the filtered irAVP, 48 +/- 4.8% was recovered in the urine. To investigate the importance of V2 receptors in the metabolism of AVP, clearance measurements were made in the presence of the V2 antagonist [d(CH2)5,D-Ile2,Ile4,Arg8]AVP (5 x 10(-9) M). Total renal clearance of irAVP was reduced by 48% to 848 +/- 79 microliters.min-1.g-1. This reduction was entirely accounted for by the complete inhibition of peritubular clearance of irAVP. In the presence of the V2 antagonist, irAVP was cleared only by filtration. The proportion of filtered AVP recovered in the urine (53 +/- 8.7%) was not significantly altered by the presence of the V2 antagonist. We conclude that a major component of the renal clearance of AVP depends on receptor-mediated uptake of AVP in the kidney cells.

Animals↗
PubMed1982

Improved function with amino acids in the isolated perfused kidney.

When isolated rat kidneys are perfused with glucose as the only substrate, there is a progressive diminution in glomerular filtration rate and fractional reabsorption of sodium. This is most marked after 1 h. Renal glutathione content rapidly falls and is less than 30% of control levels after 1 h. Renal concentrating ability is markedly impaired and structural lesions are consistently observed in cells lining the thick ascending limb of Henle's loop. Addition of 20 physiologic amino acids including cysteine to the perfusate prevents the fall in renal glutathione, prevents the anatomical damage to ascending limb cells, permits GFR and fractional sodium reabsorption to remain high and close to their initial levels for as long as 4 h, and improves renal concentrating capacity. If amino acid supplementation is limited to three precursors of glutathione--cysteine, glycine, and glutamic acid--renal glutathione content is preserved and concentrating ability is improved, but GFR and fractional sodium reabsorption are not maintained as well as with comprehensive amino acid supplements. The results suggest that amino acid deficiency and glutathione depletion may contribute to disturbances in renal structure and function.

Absorption↗
PubMed1978

Catabolism of the apoprotein of low density lipoproteins by the isolated perfused rat liver.

Isolated rat livers were perfused for 4 hours in a recirculating system containing washed rat erythrocytes. Biologically screened, radioiodinated low density lipoproteins (1.030 < d < 1.055 g/ml) were added to the perfusate with different amounts of whole serum to supply unlabeled rat low density lipoproteins. Apolipoprotein B contained 90% of the bound (131)I, other apolipoproteins contained 4%, and lipids contained the remainder. The fraction of apolipoprotein mass degraded during the perfusion was quantified by the linear increment of non-protein-bound radioiodine in the perfusate, corrected for the increment observed during recirculation of the perfusate in the absence of a liver. The fractional catabolic rate ranged from 0.3 to 1.7%/hr in seven experiments and was inversely related to the size of perfusate pool of low density apolipoprotein. The catabolic rate of low density apolipoprotein (fractional catabolic rate x pool size) in four livers, in which the concentration of rat low density lipoproteins was 50-100% of that present in intact rats, was 5.3 +/- 2.7 micro g hr(-1) (mean +/- SD). Similar results were obtained with human low density lipoproteins. These rates were compared with catabolic rates for the apoprotein of rat low density lipoproteins in intact animals. Fractional catabolic rate in vivo, obtained by multi-compartmental analysis of the disappearance curve of (131)I-labeled low density apolipoprotein from blood plasma, was 15.2 +/- 3.1% hr(-1) (mean +/- SD). Total catabolic rate in vivo (fractional catabolic rate x intravascular pool of low density apolipoprotein) was 76 +/- 14 micro g hr(-1) (mean +/- SD). The results suggest that only a small fraction of low density apolipoprotein mass in rats is degraded by the liver.

Animals↗
PubMed1983

Age dependent phagocytosis of red cell membranes by the reticulohistiocytary system of the isolated perfused rat liver.

Isolated rat livers were perfused with a medium free of immune globulines, protein and hemoglobin to investigate age-dependent differences in the phagocytosis of erythrocyte membranes. Membranes of young erythrocytes were phagocytised in a significantly higher rate than those of old ones. The control parameters of the liver function were also significantly higher during the increased phagocytosis of the young cells than that of old cells and cells of the control group.

Aging↗
PubMed1984

Insulin and cortisol improve heat tolerance in isolated perfused rat liver.

Isolated rat livers were perfused at 37 degrees, 41 degrees, 42 degrees, and 43 degrees C with and without insulin and cortisol. Two additional groups were perfused at 42 degrees C with either hormone alone. The perfusate contained red blood cells, amino acids, and albumin in Krebs-Ringer bicarbonate. Bile flow was significantly increased by hormones at 37 degrees C. Bile flow was also increased by hormones at all other temperatures. At 41 degrees C, K+ leakage was the only parameter that indicated injury. Insulin and cortisol significantly reduced K+ leakage at this temperature compared to those without hormones. At 42 degrees C, insulin and cortisol reduced K+ leakage, increased bile flow, reduced transaminase release, and improved ultrastructural integrity. The enhanced bile flow was due primarily to insulin. A reduction in K+ leakage required both insulin and cortisol. Transaminase leakage responded to either hormone alone or in combination; however, only the cortisol-treated group showed a statistically significant reduction in transaminase leakage. At 43 degrees C, indications of irreversible injury were evident and hormones had no beneficial effects. Loss of membrane homeostasis appeared to be the initial event.

Alanine Transaminase↗
PubMed1995

Role of corticosterone in TNF and IL-6 production in isolated perfused rat liver.

Using an isolated perfused rat liver (IPRL) preparation, we assessed whether corticosterone may contribute to the rise in tumor necrosis factor (TNF) and interleukin-6 (IL-6) in rats after injection with lipopolysaccharide (LPS) or exposure to psychological stress. Intravenous infusion of LPS into the IPRL led to dose-dependent increases in TNF and IL-6 concentrations in the effluent. Anisomycin, a protein synthesis inhibitor, completely blocked the rise in TNF and IL-6 concentration in the IPRL effluent, supporting the hypothesis that the synthesis (or release) of these cytokines was dependent on protein synthesis. Intravenous infusion of corticosterone at nonstressed (35 ng/ml) and stressed levels (350 ng/ml) increased TNF and/or IL-6 release. However, when LPS was combined with corticosterone, the lower dose of corticosterone facilitated the release of cytokines, whereas the higher dose of corticosterone suppressed the release of cytokines. We then showed that isolated Kupffer cells were capable of significant TNF and IL-6 production and that corticosterone decreased LPS-induced cytokine production in these cells. Our data support the hypothesis that the liver is an important source of circulating cytokines in response to LPS. In addition, although in vitro data generally support the hypothesis that corticosterone suppresses the production of cytokines, our in situ data support the hypothesis that physiological levels of corticosterone cause an increase in TNF and IL-6.

Animals↗