The influence of hormones and inflammatory agents on C-reactive protein, cortisol and alanine aminotransferase in the plaice (Pleuronectes platessa L.)

Endotoxin stimulates production of both C-reactive protein (CRP) and cortisol in the plaice within 24 hr. Cortisol alone (optimum dose i.p. 500 micrograms/300 g wt fish) also stimulates CRP production and the possibility that endotoxin acts through cortisol was examined. Dexamethasone suppresses cortisol production but elevates CRP. Cortisol levels are restored to normal within 24 hr of endotoxin injection. Turpentine and ACTH which stimulate cortisol do not affect CRP. Endotoxin and cortisol have no significant effect on alanine aminotransferase activity in the serum and liver although it is elevated in the serum within 24 hr of the administration of adrenalin or turpentine.     

Triiodothyronine and vitamin A-deficiency in the rat

The total (TT3) and free serum triiodothyronine (fT3) and the distribution of a tracer dose of 125I-T3 were studied in rats on a vitamin A-deficient diet. After 6 weeks on the diet there was an increased serum T3 (TT3 and fT3). But after injection of 125I-T3 a smaller radioactivity was counted in kidney and liver of deficient animals, thus revealing a smaller transport of T3 into the target cells. So vitamin A-deficiency induces an original hormonal status responsible for the conflicting metabolic changes already described in deficient rats.     

Hydrocarbon metabolism and cortisol balance in oil-exposed ringed seals, Phoca hispida

1. Ringed seals were exposed experimentally to oil contamination, by feeding of a [14C]naphthalene marked crude oil in fish for up to 4 days at a rate of 5 ml/day. 2. Mixed function oxygenase (MFO) activity, measured as aryl hydrocarbon hydroxylase in liver and kidney, was found to be induced, in particular in kidney tissue where the activity increased 3-fold. 3. MFO induction correlated with a high degree of conversion of crude oil hydrocarbons to water-soluble metabolites. Most of the radioactivity was found in the polar fraction of plasma and urine. 4. Plasma cortisol levels were somewhat elevated by captive holding, and increased markedly after oil-exposure. Cortisol half-life decreased after oil exposure from 1 3/4 to 1 hr.     

The effect of cortisol on thyroid hormone kinetics in the ovine fetus

The mechanism underlying the association of rising concentrations of circulating triiodothyronine (T3) with the prepartum surge in the concentration of cortisol was investigated in 11 fetal sheep. The concentrations and metabolic clearance rates of T3 and thyroxine (T4) were measured prior to and following a continuous intravascular infusion of cortisol (1 mg/h for 84 h). Mean plasma T3 concentrations increased 10-fold following cortisol infusion whereas the concentrations of T4 either remained stable or exhibited a variable decline. Cortisol induced a 5-fold decrease in the metabolic clearance rate of T3 and a 6-fold increase in that of T4. The corresponding mean production rates of T3 and T4 increased significantly although the magnitude of the change varied between fetuses. We conclude that the prepartum rise in plasma T3 concentrations is likely to be a consequence of both a decreased metabolic clearance of T3 and increased peripheral conversion of T4 to T3 caused by rising concentrations of cortisol in fetal plasma.     

Preliminary study on the effect of temperature on the transport of thyroxine (T4) into the body tissues and sub-cellular fractions of liver and muscle of carp, Cyprinus carpio

In order to determine if the inability of thyroxine to induce cellular effects at low temperature is mediated through a temperature-sensitive system for the translocation of T4 into the nucleus, the effect of temperature on the uptake of T4 by body tissues and sub-cellular fractions of carp liver and muscle was studied in vivo. A single injection of 125I-T4 (1 micro C/10 g body weight) was given intraperitoneally to juvenile carp maintained at 15 and 25 C. Uptake from the peritoneal cavity was rapid. All the tissues exhibited maximum radioactivity at 2 hour after the injection. Fish kept at 25 C showed another peak at 8 hour and those at 15 C at 48 hour after the single injection. Transfer of T4 from the cytoplasm to nuclei was not blocked at lower temperatures. For example, in liver at 8 hour, nuclei from fish tissues kept at lower or higher temperatures had equal amounts of radioactivity. Muscle nuclei had 15% more radioactivity than liver nuclei when expressed as radioactivity/g tissue. Since there are comparable amounts of activity in the nuclei at both temperatures, some other mechanism/s than a simple block in transport from cytoplasm to nuclei is operating. There are some indications that nutritional status of fish may be playing some role in this respect.     

Glucose metabolism in the newborn rat. Hormonal effects in vivo

1. The concentrations of liver glycogen and plasma d-glucose were measured in caesarian-delivered newborn rats at time-intervals up to 3h after delivery after treatment of the neonatal rats with glucagon, dibutyryl cyclic AMP, cortisol or cortisol+dibutyryl cyclic AMP. Glycogenolysis was promoted by glucagon or dibutyryl cyclic AMP in the third hour after birth but not at earlier times. Cortisol and dibutyryl cyclic AMP together (but neither agent alone) promoted glycogenolysis in the second hour after birth, but no hormone combination was effective in the first postnatal hour. 2. The specific radioactivity of plasma d-glucose was measured as a function of time for up to 75 min after the intraperitoneal injection of d-[6-(14)C]glucose and d-[6-(3)H]glucose into newborn rats at delivery and after treatment with glucagon or actinomycin D. Glucagon-mediated hyperglycaemia at this time was due to an increased rate of glucose formation and a decreased rate of glucose utilization. Actinomycin D prevented glucose formation and accelerated the rate of postnatal hypoglycaemia. 3. The specific radioactivity of plasma l-lactate and the incorporation of (14)C into plasma d-glucose was measured as a function of time after the intraperitoneal injection of l-[U-(14)C]lactate into glucagon- or actinomycin D-treated rats immediately after delivery. The calculated rates of lactate formation were unchanged by either treatment, but lactate utilization was stimulated by glucagon administration. Glucagon stimulated and actinomycin D diminished (14)C incorporation into plasma d-glucose. 4. The factors involved in the initiation of glycogenolysis and gluconeogenesis in the rat immediately after birth are discussed.     

Plasma thyroxine and cortisol under basal conditions and during cold stress in the aging dog

The effects of aging on plasma concentration of thyroxine (T4) and cortisol and on responses of these hormones to low ambient temperatures were determined in the dog. Female beagle dogs were divided into three age groups: old, adult, and puppies. The mean (+/- SD) ages were 11.4 +/- 0.2 years, 3.0 +/- 0.4 years, and 7.6 +/- 0.2 weeks, respectively. All dogs came from a genetically homogeneous colony and were free from any disease. The adult and old dogs were used during anestrus. Based on four daily blood samples, the mean (+/- SE) T4 level in the old dogs (2.8 +/- 0.1 microgram/dl) was significantly (P less than 0.001) lower than that in the adults (4.2 +/- 0.2 micrograms/dl) and puppies (4.4 +/- 0.2 micrograms/dl). By contrast, mean plasma cortisol levels in the old dogs (21.1 +/- 3.1 ng/ml) and adults (15.4 +/- 2.4 ng/ml) were significantly higher than those in the puppies (7.2 +/- 1.1 ng/ml). No significant changes in plasma T4 and cortisol occurred in any of the three age groups at 22 degrees C or during exposure to 10 or 4 degrees C. Exposure to -5 degrees C, however, produced significant increases in T4 (greater than 130% by 5 hr) and cortisol (greater than 280% by 1 hr) in adult dogs. This temperature produced only a modest increase in T4 (70% by 3.5 hr) and no change in cortisol in the old dogs. The puppies showed no change in T4 and cortisol during exposure to -5 degrees C. The results demonstrate that with advancing age, plasma T4 and cortisol concentrations change in opposite directions, thus supporting the hypothesis of a negative relationship between these two hormones. These results also show that the responses of these hormones to the stress of cold decline during aging and are not yet developed in the very young.     

Time course of distribution to tissues of 125I-somatomedin A injected into the rat

125I-somatomedin A (SMA) was injected iv into rats. Distribution studies in rats showed concentrations of radioactivity to be high in kidney and plasma, low in brain, and intermediate in other tissues. The concentration of total and trichloracetic acid (TCA) precipitable radioactivity in rat blood and tissues fell at rapid rate. Ninety per cent of the radioactivity was in the urine in 24 hr, and only 15% of urine radioactivity was TCA precipitable. The half-life of the radioactivity in TCA-precipitable fraction from blood and that from tissues were nearly identical (about 6 hr). In both liver and kidney, TCA-precipitable radioactivity was detected in membrane and/or organellar fraction and cytosol fraction. Sephadex G-200 chromatography at neutral PHY AT NEUTRAL PH of plasma after injection of 125I-SMA revealed 3 peaks of radioactivity in higher molecular weight region than purified SMA.     

Specific receptors for triiodothyronine in nuclei isolated from normal human polynuclear neutrophils

In normal subjects, nuclei isolated and purified from circulating granulocytes bound 125I-T3. Binding was reversible and inhibited by unlabelled hormone. Scatchard plots showed a single class of high affinity sites (Kd: approximately 1,5 nM) with a high maximal binding capacity (MBC: approximately 400 fmol of T3 bound/100 micrograms of DNA). Structural analogs partially competed with 125I-T3 binding. These data suggest that human normal polymorphonuclear neutrophils possess specific nuclear receptors for triiodothyronine.     

Cortisol-induced CXCR4 augmentation mobilizes T lymphocytes after acute physical stress

The aim of this study was to elucidate the mechanism responsible for lymphopenia after exercise. Seven young healthy men volunteered for this study. Peripheral blood mononuclear cells (PBMC) were cultured with cortisol and analyzed for C-X-C motif chemokine receptor 4 (CXCR4) expression by flow cytometry. To determine the effects of exercise, subjects performed exhaustive cycling exercise. PBMC were cultured with plasma obtained before and after the cycling exercise. Alternatively, PBMC obtained before and after exercise were cultured without plasma or glucocorticoid to examine whether PBMC were primed in vivo for CXCR4 expression. We analyzed cortisol- or plasma-treated PBMC to determine their ability to migrate through membrane filters in response to stromal cell-derived factor 1alpha/CXCL12. Cortisol dose- and time-dependently augmented CXCR4 expression on T lymphocytes, with <6 h of treatment sufficient to augment CXCR4 on T lymphocytes. Postexercise plasma also augmented CXCR4 expression. Cortisol or postexercise plasma treatment markedly enhanced migration of T lymphocytes toward CXCL12. Augmentation of CXCR4 on T lymphocytes by cortisol or plasma was effectively blocked by the glucocorticoid receptor antagonist RU-486. Thus exercise-elicited endogenous cortisol effectively augments CXCR4 expression on T lymphocytes, which may account for lymphopenia after exercise.     

A suppression of gonadotropin secretion by cortisol in castrated male rhesus monkeys (Macaca mulatta) mediated by the interruption of hypothalamic gonadotropin-releasing hormone release

Four orchidectomized rhesus monkeys (3-3.5 yr of age) were treated for 62 days with daily i.m. injections of hydrocortisone acetate (HCA) at a dose of 10-20 mg/(kg BW X day), and blood samples were obtained daily or every other day before, during, and after treatment. Hydrocortisone acetate injections resulted in a progressive rise in mean plasma cortisol from basal concentrations of 17-35 micrograms/100 ml prior to initiation of steroid treatment to approximately 150 micrograms/100 ml 5 wk later. When serum cortisol concentrations reached 100 micrograms/100 ml, 3-4 wk after the initiation of HCA treatment, circulating luteinizing hormone (LH) and follicle-stimulating hormone (FSH) began to decline, reaching nondetectable concentrations 35 days later. Withdrawal of HCA resulted in a return in plasma cortisol concentrations to pretreatment control levels, which was associated with a complete restoration of gonadotropin secretion. In 2 animals, administration of an intermittent i.v. infusion of gonadotropin-releasing hormone (GnRH) (0.1 micrograms/min for 3 min once every hour), which appears to stimulate the gonadotropes in a physiologic manner, reversed the cortisol-induced inhibition of gonadotropin secretion, restoring circulating LH and FSH concentrations to within 80-100% of control. These results suggest that, in the rhesus monkey, the major site of the inhibitory action of cortisol on gonadotropin release resides at a suprapituitary level and is mediated by interruption of hypothalamic GnRH release.     

半胱胺对断奶前后仔猪血清皮质醇、T3、T4和IL-2水平的影响

选取新生仔猪18窝,随机分为对照组和处理组各9窝。从12日龄开始,对照组饲喂基础乳猪料;处理组在基础乳猪料中添加半胱胺,剂量为120mg／kg饲料。两组仔猪均在35日龄断奶。分别于断奶前7d(28日龄,D28),断奶当天(D35),断奶后36h(D36．5)、72h(D38)、7d(D42)、10d(D45),随机选取对照组和处理组仔猪各6头,屠宰采集血样。采用放射免疫分析法测定仔猪血清皮质醇、三碘甲腺厚氨酸(T3)、甲状腺激素(T4)和白细胞介素-2(IL-2)水平。结果表明：(1)对照组血清皮质醇水平在断奶前保持稳定,在D36．5时升高,在D42时恢复至D35水平,随后保持稳定;处理组血清皮质醇水平在D36．5时较D35有升高趋势,在D38时恢复至D35水平,随后保持稳定。对照组血清T3水平在D36．5显著高于D28,其他日龄点间无显著差异,处理组基本保持稳定。对照组血清T4水平在D36．5时升高,在D38日时恢复至D35水平,随后保持稳定;处理组血清T4水平从D35至D45基本保持稳定。两组中血清IL-2水平在D28至D42保持稳定,D45升高。(2)在D36．5时,处理组血清皮质醇水平较对照组降低30％,处理组血清T3水平在D35和D45较对照组提高49．2％和38．6％,T4水平在D35和D45提高31％和45．8％,在其他日龄点,处理组T3、T4水平较对照组有升高趋势,但差异不显著。处理组IL-2水平在D36．5、D38、D45也分别较对照组提高22．1％、12．6％和17．8％,在其他日龄点有升高趋势。以上结果提示半胱胺能抵抗仔猪断奶应激,提高仔猪血清T3、T4水平,增强仔猪的免疫力。     

Growth hormone stimulates the peripheral conversion of thyroxine into triiodothyronine by increasing the liver 5'-monodeiodinase activity in the fasted and normal fed chicken

Normal fed and 2 days fasted Warren chickens were injected intravenously with 100 micrograms of ovine growth hormone (GH) and ovine prolactin and plasma concentrations of thyroid hormones were assayed prior and up to 2 h after injection. Fasting alone decreases T3, but increases T4. An injection of GH resulted in increases of plasma T3 concentrations in two fasting experiments by 40% (after 3/4 h) and 104% (after 1 h). In normal fed animals no increase is observed in the first experiment, whereas a 35% increase occurs in the second one. An injection of 100 micrograms prolactin does not influence T3 in normal fed or fasting animals. Both GH and prolactin, however, may decrease plasma concentrations of T4. In a separate experiment 50 micrograms and 200 micrograms of GH raised the decreased T3 levels after fasting by 39% and 60% respectively 1 h after injection and by 24 and 61% respectively in normal fed chicken, whereas prolactin was ineffective in this regard. Using Hisex chickens, the influence of an injection of 100 micrograms GH on plasma concentrations of thyroid hormones could be confirmed. At the same time GH increases the liver 5'-monodeiodinase activity by 330% after 1 h and by 147% after 2 h. The peroxidase activity is not influenced in normal fed chickens, but GH decreases this activity in food deprived animals after 1 h and 2 h. It is concluded that ovine GH, but not prolactin, stimulates the peripheral conversion of T4 into T3 in both normal fed and food deprived chicken and that this effect is dose dependent.     

Temperature shifts induce the selective loss of alveolar-macrophage plasma membrane components

A shift in the incubation temperature of rabbit alveolar macrophages (0 degree C leads to 37 degrees C leads to 0 degree C) resulted in a 40-60% reduction in the ability of cells to bind alphamacroglobulin. 125I-trypsin complexes (alphaM. 125I-T). The reduction in binding activity did not reflect a disruption of cell integrity since the levels of intracellular components (lactate dehydrogenase, beta-N-acetyl-hexosaminidase) or other plasma membrane components (alkaline phosphodiesterase) were unaltered. Analysis of receptor-ligand interaction indicated that the temperature shift effected a decline in receptor number rather than an alteration in ligand-receptor affinity. Studies indicated that a temperature shift resulted in the loss of unoccupied receptors, and that ligand bound to receptors was not lost. However, after ligand internalization, receptors were removed by the temperature shift. The rate of receptor loss was maximal when cells were incubated at temperatures greater than 24 degrees C. Receptor loss was not prevented by treatment of cells with colchicine, cytochalasin B, or N-ethylamaleimide, but was prevented by treatment with the cross-linking agent paraformaldehyde. Data indicate that the reduction in alphaM. 125I-T binding activity resulted from shedding of receptors into the media since media obtained from temperature-shifted cells contained material that competed with cell-bound receptors for alphaM. 125I-T. Additionally, binding of alphaM. 125I-T was diminished on membrane fragments obtained from temperature-shifted cells. Incubation with Triton X-100, of cells whose receptors were occupied with alphaM. 125I-T, led to the extraction of 40% of cell-bound activity. However, no radioactivity was extracted from cells labeled with alphaM. 125I-T after a temperature shift. Measurement of ligand accumulation by control and temperature-shifted cells incubated at 20 degrees C indicated that control cells exhibited a subpopulation of receptors capable of binding ligand but only slowly internalizing it. This subpopulation was not present on temperature-shifted cells. These results indicate that surface receptors for alphamacroglobulin . protease complexes are heterogeneous and that the temperature shift resulted in the selective loss of membrane components.     

The metabolism of human sex hormone-binding globulin in the rhesus monkey.

The metabolism of human sex hormone-binding globulin (hSHBG) was studied in eight female rhesus monkeys (Macaca mulatta) after the pulse injection of [125I]-hSHBG. hSHBG was iodinated with 125I using a chloramine T technique, and the [125I]-hSHBG was separated from other constituents by molecular sieve chromatography with a Sephadex G-25 column. The [125I]-hSHBG was administered intravenously as a pulse in 2 ml of phosphate buffer, pH 7.4, to each of eight rhesus monkeys. Blood samples (2.0 ml) were obtained at 2, 4, 6, 8, 24, 30, 45, and 54 hr after the injection. The glycoproteins were precipitated with concanavalin A-Sepharose, and the radioactivity was measured. The concentration of radioactivity as fraction of dose/ml of serum was plotted on a semilog scale against time. The disappearance of radioactivity could be expressed best as the sum of two exponentials, with a mean +/- SE t1/2 of 2.5 +/- 0.4 and 33.1 +/- 3.7 hr, respectively. The initial volume of distribution was 461 +/- 78 ml and the metabolic clearance rate was 559 +/- 66 ml/day. The very low clearance rate and prolonged t1/2 are compatible with a relative stability in the circulating mass of SHBG. Rapid changes in concentration of SHBG could be due to changes in serum volume, reversible changes in tissue distribution of SHBG, or the secretion of variable forms of desialylated SHBG.     

Type II iodothyronine deiodinase provides intracellular 3,5,3'-triiodothyronine to normal and regenerating mouse skeletal muscle

The FoxO3-dependent increase in type II deiodinase (D2), which converts the prohormone thyroxine (T(4)) to 3,5,3'-triiodothyronine (T(3)), is required for normal mouse skeletal muscle differentiation and regeneration. This implies a requirement for an increase in D2-generated intracellular T(3) under these conditions, which has not been directly demonstrated despite the presence of D2 activity in skeletal muscle. We directly show that D2-mediated T(4)-to-T(3) conversion increases during differentiation in C(2)C(12) myoblast and primary cultures of mouse neonatal skeletal muscle precursor cells, and that blockade of D2 eliminates this. In adult mice given (125)I-T(4) and (131)I-T(3), the intracellular (125)I-T(3)/(131)I-T(3) ratio is significantly higher than in serum in both the D2-expressing cerebral cortex and the skeletal muscle of wild-type, but not D2KO, mice. In D1-expressing liver and kidney, the (125)I-T(3)/(131)I-T(3) ratio does not differ from that in serum. Hypothyroidism increases D2 activity, and in agreement with this, the difference in (125)I-T(3)/(131)I-T(3) ratio is increased further in hypothyroid wild-type mice but not altered in the D2KO. Notably, in wild-type but not in D2KO mice, the muscle production of (125)I-T(3) is doubled after skeletal muscle injury. Thus, D2-mediated T(4)-to-T(3) conversion generates significant intracellular T(3) in normal mouse skeletal muscle, with the increased T(3) required for muscle regeneration being provided by increased D2 synthesis, not by T(3) from the circulation.     

A case of hypothyroidism with simultaneous presence of stimulating type anti-thyrotropin (TSH) receptor antibodies and anti-thyroxine (T4) autoantibodies.

We have examined a hypothyroid patient with stimulating type anti-thyrotropin (TSH) receptor antibodies and without blocking type anti-TSH receptor antibodies. Although she had high serum TSH (240 microU/ml) and low free triiodothyronine (FT3, 0.49 pg/ml) concentrations, which agree with physical findings of hypothyroidism, she had an unusually high free thyroxine (FT4) concentration (3.56 ng/dl). Incubation of her serum with 125I-T4, followed by precipitation with 12.5% polyethylene glycol (PEG) disclosed a higher binding of 125I-T4 (34.4%) than in normal controls, being 5-7%. In addition, binding of 125I-T4 to her serum gamma-globulin was completely displaced by the addition of unlabelled T4. From these results it was concluded that her serum contained anti-T4 autoantibodies. Treatment with synthetic T4 was begun and her thyroid function was monitored by sensitive TSH radioimmunoassay (RIA) and RIA of FT4 after PEG treatment. Since both sensitive TSH RIA and FT4 RIA results after PEG treatment give results concordant with the physical findings, it was concluded that both of the RIA results are useful for the evaluation of thyroid function in patients with thyroid hormone autoantibodies.     

Brain HSP70 mRNA expression is linked with plasma cortisol levels in goldfish (Carassius auratus) exposed to a potential predator

We previously found that when goldfish were exposed to a potential predator, bluegills, the goldfish experienced an increase in HSP70 mRNA expression in the brains and increased plasma cortisol levels. In the present study, we examined the potential causative relationship between HSP70 mRNA expression and plasma cortisol levels. Cortisol agonists (corticotropin releasing factor and cortisol) and antagonists (metyrapone and betamethasone) were used to modulate plasma cortisol levels. HSP70 mRNA expression and plasma cortisol levels were analyzed by Northern blotting and ELISA, respectively. Goldfish treated with the cortisol agonists showed marked increases in plasma cortisol levels and also in brain HSP70 mRNA expression. When goldfish were exposed to bluegills, plasma cortisol levels increased and HSP70 mRNA expression was enhanced after 6 hr. However, pre-treatment with the cortisol antagonists 24 hr prior to the exposure inhibited the enhancement as well as the increase in plasma cortisol levels. These results suggest that plasma cortisol plays a key role in the enhancement of brain HSP70 mRNA expression in goldfish stressed by exposure to bluegills.     

Cortisol and aldosterone comparisons of cottontail rabbits collected by shooting, trapping, and falconry

Cortisol and aldosterone levels were measured in plasma of eastern cottontail rabbits (Sylvilagus floridanus) collected by three different methods, i.e., shooting, live-trapping and falconry. Cortisol levels ranged from near 0 to 27.5 micrograms/100 ml and aldosterone from near 0 to 220 ng/100 ml. Shot animals had significantly lower cortisol concentrations than those taken by either of the other methods. Trapped cottontails also had significantly lower aldosterone levels.     

Pharmacodynamic and protective properties of a murine lipopolysaccharide-specific monoclonal antibody in experimental Pseudomonas aeruginosa pneumonia in mice.

We employed a Pseudomonas aeruginosa mouse pneumonia model to evaluate the ability of a murine monoclonal antibody (MAb) specific for the O-side chain of P. aeruginosa Fisher Immunotype-1 lipopolysaccharide (LPS) to achieve and sustain therapeutic levels in plasma and lung tissue, reduce bacterial populations in the lung, and prevent pneumonia-associated mortality. An IgG3 MAb (Y1-5A4) administered to mice i.v. over a dose range of 125-1,000 micrograms/mouse produced plasma and lung tissue levels at 2 hr of 61-507 micrograms/ml and 4.3-150 micrograms/g, respectively. The 1,000 micrograms MAb dose reduced bacterial counts in lung tissue (log10 cfu/g +/- S.D.) and blood (log10 cfu/ml +/- S.D.) 20 hr post-treatment (18 hr post-challenge) from 10.00 +/- 0.66 to 7.66 +/- 0.91 (P less than 0.01) and from 4.39 +/- 0.81 to less than 3.0, respectively. Administration of MAb to mice in doses of 125-500 micrograms 2 hr prior to a 3 x 50% lethal bacterial challenge produced significant protection against death, with a calculated 50% protective dose of 167 micrograms. Protection was noted following administration of 1,000 micrograms of MAb up to 6 hr after bacterial challenge (P less than 0.05, compared with untreated control). Histological examination of lung tissue from infected mice revealed less acute inflammation, necrosis, and hemorrhage in MAb-treated compared with untreated control animals and greater localization of Pseudomonas antigen within the phagocytic cells in alveolar space. These findings document the in vivo therapeutic efficacy of an LPS-specific IgG MAb in a murine model of acute P. aeruginosa pneumonia, based in part upon the achievability of effective MAb concentrations in plasma and lung tissue.