Protective effect of low-power laser radiation in acute toxic stress

The effect of preliminary short-term irradiation with He-Ne laser light (632.8 nm, 0.2 mW/cm2) of the thymus zone projection of male NMRI mice subjected to acute toxic stress on the responses of immune cells was studied. Stress was modeled by lipopolysaccharide injection, 250 mg/100 g of body weight, which induced a significant increase in the production of several macrophage cytokines, IL-1alpha, IL-1beta, IL-6, IL-10 and TNF-alpha. A single irradiation with laser light did not provoke considerable variations in NO production in cells but induced an enhancement in the production of heat shock proteins Hsp25, Hsp70, and Hsp90. Nevertheless, when irradiation with red laser light was applied prior to toxic stress, considerable normalization of production of nearly all cytokines studied and nitric oxide was observed. Moreover, the normalization of production of heat shock proteins has been shown in these conditions. Thus, preliminary exposure of a small area of animal skin surface provoked a significant lowering in the toxic effect of lipopolysaccharide.     

COX-2 inhibition attenuates anorexia during systemic inflammation without impairing cytokine production

Anorexia and weight loss are frequent complications of acute and chronic infections and result from induction of cytokines, prostaglandins, and other inflammatory mediators that are critical for pathogen elimination. Selective attenuation of the hypophagic response to infection and maintenance of the production of factors essential for infection control would be a useful addition to antimicrobial therapy in the treatment of human disease. Here, we evaluate the relative contribution of cyclooxygenase (COX)-1- and COX-2-derived prostaglandins to anorexia and weight loss precipitated by systemic immune activation by lipopolysaccharide (LPS). Using COX isoform-selective pharmacological inhibitors and gene knockout mice, we found that COX-2 inhibition during LPS-induced inflammation results in preserved food intake and maintenance of body weight, whereas COX-1 inhibition results in augmented and prolonged weight loss. Regulation of neuropeptide Y, corticotropin-releasing hormone, leptin, and interleukin-6 does not change as a function of COX-2 inhibition after LPS administration. Our data implicate COX-2 inhibition as a therapeutic target to maintain nutritional status while still allowing a normal cytokine response during infection.     

Plasma Luteinizing Hormone Response to Increasing doses of Synthetic Gonadotrophin-Releasing Hormone in Heifers

The dosenresponse relationship for a synthetic gonadotrophin-releasing hormone (GnRH) was studied in normally cycling heifers using the area under the luteinizing hormone (LH) curve as a response parameter. Oestrus was synchronized by an injection of 0.5 mg cloprostenol before the experiment started and after the 3rd treatment with GnRH. Treatment with GnRH as assigned in a Latin square included 5 dose levels (0, 10, 50, 100, 250 μg) and 5 treatment days over a period of 22 days. GnRH was capable of inducing an increase of plasma LH within 30 min after injection. Plasma LH response increased with increasing doses of GnRH, the largest increase being observed when the dose was raised from 50 μg to 100 μg. One heifer did not respond to any of the doses applied. The existence of an individual treshold dose of GnRH is suggested.     

Skeletal muscle PGC-1α is required for maintaining an acute LPS-induced TNFα response

Many lifestyle-related diseases are associated with low-grade inflammation and peroxisome proliferator activated receptor γ coactivator (PGC)-1α has been suggested to be protective against low-grade inflammation. However, whether these anti-inflammatory properties affect acute inflammation is not known. The aim of the present study was therefore to investigate the role of muscle PGC-1α in acute inflammation. Quadriceps muscles were removed from 10-week old whole body PGC-1α knockout (KO), muscle specific PGC-1α KO (MKO) and muscle-specific PGC-1α overexpression mice (TG), 2 hours after an intraperitoneal injection of either 0.8 μg LPS/g body weight or saline. Basal TNFα mRNA content was lower in skeletal muscle of whole body PGC-1α KO mice and in accordance TG mice showed increased TNFα mRNA and protein level relative to WT, indicating a possible PGC-1α mediated regulation of TNFα. Basal p65 phosphorylation was increased in TG mice possibly explaining the elevated TNFα expression in these mice. Systemically, TG mice had reduced basal plasma TNFα levels compared with WT suggesting a protective effect against systemic low-grade inflammation in these animals. While TG mice reached similar TNFα levels as WT and showed more marked induction in plasma TNFα than WT after LPS injection, MKO PGC-1α mice had a reduced plasma TNFα and skeletal muscle TNFα mRNA response to LPS. In conclusion, the present findings suggest that PGC-1α enhances basal TNFα expression in skeletal muscle and indicate that PGC-1α does not exert anti-inflammatory effects during acute inflammation. Lack of skeletal muscle PGC-1α seems however to impair the acute TNFα response, which may reflect a phenotype more susceptible to infections as also observed in type 2 diabetes patients.     

Endotoxin rapidly induces changes in lipid metabolism that produce hypertriglyceridemia: low doses stimulate hepatic triglyceride production while high doses inhibit clearance.

Hyperlipidemia frequently accompanies infectious diseases and may be due to increases in lipoprotein production or decreases in lipoprotein clearance. The administration of endotoxin (LPS) has been used to mimic infection and prior studies demonstrate that LPS produces hypertriglyceridemia. In the present study in rodents, the dose of LPS necessary to induce hyperlipidemia was orders of magnitude less than that necessary to induce shock and death. As little as 10 ng/100 g body weight induced hypertriglyceridemia and this increase in serum triglyceride levels occurred rapidly (78% increase at 2 h). At high doses of LPS (50 micrograms/100 g body weight), the clearance of triglyceride-rich lipoproteins was decreased. At low doses of LPS (100 ng/100 g body weight), triglyceride clearance was not altered but the hepatic secretion of triglyceride was increased. Low dose LPS stimulated hepatic de novo fatty acid synthesis and lipolysis, both of which provided a source of fatty acids for the increase in hepatic triglyceride production. High dose LPS did not increase hepatic fatty acid synthesis or peripheral lipolysis, and hepatic triglyceride secretion was not stimulated. Thus, low dose LPS produces hypertriglyceridemia by increasing hepatic lipoprotein production, while high dose LPS produces hypertriglyceridemia by decreasing lipoprotein catabolism. Administration of anti-tumor necrosis factor (TNF) antibodies or interleukin 1 (IL-1) receptor antagonist did not prevent the increase in serum triglyceride levels induced by LPS. However, anti-TNF antibodies and interleukin 1 receptor antagonist (IL-1ra) blocked the increase in serum triglycerides induced by TNF or IL-1, respectively. These data suggest that neither of these cytokines is absolutely required for the increase in serum triglycerides induced by LPS, raising the possibility that other cytokines, small molecular mediators, or LPS itself may play a crucial role.     

Differential inflammatory response to inhaled lipopolysaccharide targeted either to the airways or the alveoli in man

Endotoxin (Lipopolysaccharide, LPS) is a potent inducer of inflammation and there is various LPS contamination in the environment, being a trigger of lung diseases and exacerbation. The objective of this study was to assess the time course of inflammation and the sensitivities of the airways and alveoli to targeted LPS inhalation in order to understand the role of LPS challenge in airway disease.In healthy volunteers without any bronchial hyperresponsiveness we targeted sequentially 1, 5 and 20 μg LPS to the airways and 5 μg LPS to the alveoli using controlled aerosol bolus inhalation. Inflammatory parameters were assessed during a 72 h time period. LPS deposited in the airways induced dose dependent systemic responses with increases of blood neutrophils (peaking at 6 h), Interleukin-6 (peaking at 6 h), body temperature (peaking at 12 h), and CRP (peaking at 24 h). 5 μg LPS targeted to the alveoli caused significantly stronger effects compared to 5 μg airway LPS deposition. Local responses were studied by measuring lung function (FEV(1)) and reactive oxygen production, assessed by hydrogen peroxide (H(2)O(2)) in fractionated exhaled breath condensate (EBC). FEV(1) showed a dose dependent decline, with lowest values at 12 h post LPS challenge. There was a significant 2-fold H(2)O(2) induction in airway-EBC at 2 h post LPS inhalation. Alveolar LPS targeting resulted in the induction of very low levels of EBC-H(2)O(2).Targeting LPS to the alveoli leads to stronger systemic responses compared to airway LPS targeting. Targeted LPS inhalation may provide a novel model of airway inflammation for studying the role of LPS contamination of air pollution in lung diseases, exacerbation and anti-inflammatory drugs.     

Assessment of the erythropoietin-producing function of the kidney and liver under controlled perfusion

The balance of erythropoietin production by the dog kidney and liver was studied during controlled normoxic perfusion. The hormone production was stimulated by acute posthemorrhagic anemia (bloodletting of 25% total blood volume) combined with subcutaneous injection of cobaltous chloride (250 microM/kg body weight). The increase in erythropoietin level was revealed in posthypoxic animal perfusate after 6 hours of perfusion. The amount of hepatic erythropoietin was shown to be 2.5 times higher than that excreted by kidneys.     

Silicon Deprivation Does Not Significantly Modify the Acute White Blood Cell Response but Does Modify Tissue Mineral Distribution Response to an Endotoxin Challenge

An experiment with rats was conducted to determine whether silicon deprivation affects the acute-phase immune response to an endotoxin challenge. Weanling female rats were assigned to two weight-matched groups of 24; one group was fed a basal diet containing about 1.9 µg Si/kg; the other group was fed the basal diet supplemented with 35 µg Si/kg as arginine silicate inositol complex. After being fed their respective diets for 8 weeks, 12 rats in each group were injected subcutaneously with 1 mg lipopolysaccharide (LPS)/kg body weight; the other 12 rats in each group were injected with deionized water. Two hours after injection, the rats were anesthetized with ether for collection of blood (for plasma), liver and femurs, and then euthanized by decapitation. LPS injection decreased total white blood cell, lymphocyte, monocyte, eosinophil, and basophil counts by 80–90%, but did not affect neutrophil counts. LPS injection also increased plasma tumor necrosis factor-α and osteopontin and decreased plasma hyaluronic acid. Silicon deprivation did not significantly affect any of these responses to LPS. Silicon in liver and silicon, iron, and zinc in femur were increased by LPS injection only in silicon-deprived rats. Silicon deprivation also increased monocyte counts and osteopontin and decreased femur zinc in rats not injected with LPS. The findings indicate that silicon deprivation does not affect the acute-immune phase decrease in inflammatory cell numbers and increase in inflammatory cytokines in response to an endotoxin challenge. Silicon deprivation, however, apparently causes slight chronic inflammation and might influence inflammatory cell proliferation in the chronic-phase inflammatory response.     

Effect of thymopentin on the production of cytokines, heat shock proteins, and NF-κB signaling proteins

In vivo effects of thymopentin, an active fragment of the naturally occurring thymic hormone thymopoietin, on the production of cytokines, nitric oxide, heat shock proteins, and signaling proteins NF-κB, phNF-κB, and IκB-α in lymphoid cells of male NMRI mice was studied. Activation of production of several cytokines (IL-1α, IL-2, IL-6, IL-10, and IFN-γ), nitric oxide, and heat shock proteins (HSP70 and HSP90) was observed in peritoneal macrophages and spleen lymphocytes of mice that received intraperitoneal injections of thymopentin (15μg per 100 g body weight). Thymopentin apparently produces stress-like rather than damaging effects. A probable action mechanism of this hormone is activation of the NF-κB signaling pathway, which is most pronounced at the NF-κB phosphorylation stage.     

Modulation of Pseudomonas aeruginosa lipopolysaccharide-induced lung inflammation by chronic iron overload in rat

Iron constitutes a critical nutrient source for bacterial growth, so iron overload is a risk factor for bacterial infections. This study aimed at investigating the role of iron overload in modulating bacterial endotoxin-induced lung inflammation. Weaning male Wistar rats were intraperitoneally injected with saline or iron sucrose [15 mg kg(-1) body weight (bw), 3 times per week, 4 weeks]. They were then intratracheally injected with Pseudomonas aeruginosa lipopolysaccharide (LPS) (5 μg kg(-1) bw) or saline. Inflammatory indices were evaluated 4 or 18 h post-LPS/saline injection. At 4 h, LPS-treated groups revealed significant increases in the majority of inflammatory parameters (LPS-binding protein (LBP), immune cell recruitment, inflammatory cytokine synthesis, myeloperoxidase activity, and alteration of alveolar-capillary permeability), as compared with control groups. At 18 h, these parameters reduced strongly with the exception for LBP content and interleukin (IL)-10. In parallel, iron acted as a modulator of immune cell recruitment; LBP, tumor necrosis factor-α, cytokine-induced neutrophil chemoattractant 3, and IL-10 synthesis; and alveolar-capillary permeability. Therefore, P. aeruginosa LPS may only act as an acute lung inflammatory molecule, and iron overload may modulate lung inflammation by enhancing different inflammatory parameters. Thus, therapy for iron overload may be a novel and efficacious approach for the prevention and treatment of bacterial lung inflammations.     

Stimulation of ornithine decarboxylase activity in rat tissues by growth hormone and by serum growth factor from rats infested with spargana of Spirometra mansonoides

Ornithine decarboxylase activity was studied in heart, kidney, liver, thymus, lung, spleen, skeletal muscle and fat of hypophysectomized rats after growth hormone treatment. A marked increase in enzyme activity was observed in kidney and liver, and a significant increase in heart and thymus at 4 h after injection of growth hormone. The kidney was the most responsive organ with an increase in activity of about 100 fold. The enzyme activity in kidney responded to a dose of 10 μg of growth hormone. Daily injection for 12 days raised activity only in the heart. Infestation for 6–13 days with spargana of Spirometra mansonoides, which also causes growth of hypophysectomized rats, increased enzyme activity in the heart and thymus. Intravenous injection of serum of hypophysectomized rats infested with spargana of Spirometra mansonoides caused a significant increase in the enzyme activity in liver and kidney after 4 h. Growth hormone and the serum growth factor of sparganosis seem to share the characteristic of causing an early increase in ornithine decarboxylase activity in rat tissues. The marked response in kidney and liver raises the possibility that these organs are the primary targets of both substances.     

Levothyroxine Dosing in Older Adults: Recommendations Derived From The Baltimore Longitudinal Study of Aging

ObjectiveAs thyroid hormone metabolism slows with advancing age, treatment dosing requirements change. Guidelines recommend titration from a low starting dose for older adults with hypothyroidism while providing weight-based estimates for younger populations. However, rapid replacement may be appropriate with acute onset of overt hypothyroidism. Therefore, a weight-based recommendation specific to older adults is needed.MethodsWe determined mean levothyroxine dose using actual and ideal body weight (IBW) ratios for the outcome of euthyroid on therapy relative to assay-specific and proposed age-specific ranges for independently living participants aged ≥65 years in the Baltimore Longitudinal Study of Aging. We examined risk factors to identify those at highest risk of overtreatment using regression analyses adjusted for potential covariables and clustering to account for multiple visits per individual.ResultsOne hundred eighty-five participants aged ≥65 years were on levothyroxine at 645 eligible visits. At euthyroid visits, participants were on an average dose of 1.09 μg/kg (1.35 μg/kg IBW), with 84% of euthyroid individuals on a dose of <1.6 μg/kg. Average euthyroid dose did not differ by sex using either actual body weight (ABW) or IBW. For obese individuals, mean euthyroid dose was lower if calculated using ABW (0.9 μg/kg vs 1.14 μg/kg; P < .01) but similar if calculated using IBW (1.42 vs 1.32 μg/kg IBW; P = .41) compared with those with a body mass index of <30.ConclusionThyroid hormone dose per body weight estimates for replacement in older adults (1.09 μg/kg ABW or 1.35 μg/kg IBW) are one-third lower than current weight-based dose recommendations for younger populations.     

Acute administration of the organochalcogen 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one induces biochemical and hematological disorders in male rats

Organochalcogens are extensively produced and employed by industry and agriculture, and the risk of occupational and environmental toxicity to them has been poorly understood. Here, we investigated the acute effect of a new organochalcogen 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one on biochemical and hematological parameters in male Wistar rats. The animals were treated with a single intraperitoneal injection of the organochalcogen at doses of 125, 250 or 500 μg·kg(-1). After 60 min, the animals were sacrificed by decapitation, and the trunk blood was collected for determination of glucose, triglycerides, cholesterol, alanine aminotransferase (ALT), aspartate aminotransferase, lactate dehydrogenase, urea, creatinine, C-reactive protein, red blood cells, hematocrit, hemoglobin and white blood cells (WBC). Our results showed a reduction in cholesterol levels in all treated groups, an increase in ALT activity at doses of 250 and 500 μg·kg(-1), a decrease of hemoglobin and an increase in WBC in animals that received 250 and 500 μg·kg(-1) of the organoselenium. In addition, we observed an increase in neutrophil counts at 125 μg·kg(-1) dose and a decrease at 500 μg·kg(-1) dose. We also verified an increase in lymphocyte counts at the dose of 500 μg·kg(-1). Thus, the present study shows that the acute treatment with this new organochalcogen causes biochemical changes and hematological disorders in male rats.     

The effects of actinomycin D,cycloheximide and puromycin on the 20-hydroxyecdysone induced autophagocytosis in larval fat body cells of Pieris brassicae

The effects of 20-hydroxyecdysone (5 μg/g body weight), cycloheximide (5 μg/g body weight), puromycin (30 μg/g body weight) and actinomycin D (30 μg/g body weight) were investigated on the larval fat body cells of 48–70-hours-old last instar larvae of Pieris brassicae.20-Hydroxyecdysone was found to induce the formation of autophagic vacuoles 3 hr after its administration, but this was, however, prevented by simultaneous cycloheximide treatment in a parallel experiment. On the contrary, puromycin proved to induce autophagocytosis. These diverse effects of the two translational inhibitors on hormone-induced autophagocytosis may be explained by differences in their modes of action.Actinomycin D, when administered 21 hr prior to the hormone, exerted a preventive effect on induced autophagocytosis, but was ineffective when applied 3 hr before the injection of 20-hydroxyecdysone.It was concluded that the presence of RNA synthesized several hours prior to the hormone treatment was a prerequisite for induction of autophagocytosis by 20-hydroxyecdysone.     

Erythropoietin augments the cytokine response to acute endotoxin-induced inflammation in humans

Recent studies have shown that erythropoietin (EPO) offers protection against ischemia, hemorrhagic shock and systemic inflammation in many tissues and it has been suggested that EPO has anti-inflammatory effects. With the aim of investigating the potential acute anti-inflammatory effects of EPO in a human in vivo model of acute systemic low-grade inflammation, we measured circulating inflammatory mediators after intravenous administration of Escherichia coli endotoxin (LPS) bolus injection (0.1 ng/kg of body weight) in young healthy male subjects. The subjects were divided into three groups receiving either (1) LPS alone, (2) EPO alone (15,000 IE of rHuEPO) or (3) EPO and LPS. Endotoxin administration alone induced a 3-, 12- and 5-fold increase in plasma concentrations of TNF-α, IL-6 and IL-10, respectively, 3 h after LPS challenge. When EPO was given prior to a bolus injection with endotoxin, the levels of TNF-α and IL-6 were enhanced by 5- and 40-fold, respectively, whereas the endotoxin-induced increase in IL-10 response was not influenced by EPO. In contrast to our hypothesis, we find that EPO augments the acute inflammatory effect.     

Central CCL2 signaling onto MCH neurons mediates metabolic and behavioral adaptation to inflammation

Sickness behavior defines the endocrine, autonomic, behavioral, and metabolic responses associated with infection. While inflammatory responses were suggested to be instrumental in the loss of appetite and body weight, the molecular underpinning remains unknown. Here, we show that systemic or central lipopolysaccharide (LPS) injection results in specific hypothalamic changes characterized by a precocious increase in the chemokine ligand 2 (CCL2) followed by an increase in pro‐inflammatory cytokines and a decrease in the orexigenic neuropeptide melanin‐concentrating hormone (MCH). We therefore hypothesized that CCL2 could be the central relay for the loss in body weight induced by the inflammatory signal LPS. We find that central delivery of CCL2 promotes neuroinflammation and the decrease in MCH and body weight. MCH neurons express CCL2 receptor and respond to CCL2 by decreasing both electrical activity and MCH release. Pharmacological or genetic inhibition of CCL2 signaling opposes the response to LPS at both molecular and physiologic levels. We conclude that CCL2 signaling onto MCH neurons represents a core mechanism that relays peripheral inflammation to sickness behavior.     

Evaluation of chronic immune system stimulation models in growing pigs

Two experiments (EXPs) were conducted to evaluate models of immune system stimulation (ISS) that can be used in nutrient metabolism studies in growing pigs. In EXP I, the pig's immune response to three non-pathogenic immunogens was evaluated, whereas in EXP II the pig's more general response to one of the immunogens was contrasted with observations on non-ISS pigs. In EXP I, nine growing barrows were fitted with a jugular catheter, and after recovery assigned to one of three treatments. Three immunogens were tested during a 10-day ISS period: (i) repeated injection of increasing amounts of Escherichia coli lipopolysaccharide (LPS); (ii) repeated subcutaneous injection of turpentine (TURP); and (iii) feeding grains naturally contaminated with mycotoxins (MYCO). In EXP II, 36 growing barrows were injected repeatedly with either saline (n = 12) or increasing amounts of LPS (n = 24) for 7 days (initial dose 60 μg/kg body weight). Treating pigs with TURP and LPS reduced feed intake (P < 0.02), whereas feed intake was not reduced in pigs on MYCO. Average daily gain (ADG; kg/day) of pigs on LPS (0.50) was higher than that of pigs on TURP (0.19), but lower than that of pigs on MYCO (0.61; P < 0.01). Body temperature was elevated in pigs on LPS and TURP, by 0.8°C and 0.7°C, respectively, relative to pre-ISS challenge values (39.3°C; P < 0.02), but remained unchanged in pigs on MYCO. Plasma concentrations of interleukin-1β were increased in pigs treated with LPS and TURP (56% and 55%, respectively, relative to 22.3 pg/ml for pre-ISS; P < 0.01), but not in MYCO-treated pigs. Plasma cortisol concentrations remained unchanged for pigs on MYCO and TURP, but were reduced in LPS-treated pigs (30% relative to 29.8 ng/ml for pre-ISS; P < 0.05). Red blood cell glutathione concentrations were lower in TURP-treated pigs (13% relative to 1.38 μM for pre-ISS; P < 0.05), but were unaffected in pigs on LPS and MYCO. In EXP I, TURP caused severe responses including skin ulceration and substantial reductions in feed intake and ADG, whereas MYCO did not induce effective ISS. In EXP II, ISS increased relative organ weights, eye temperature, white blood cell count and plasma acute-phase proteins (P < 0.05), confirming that repeated injection with increasing amounts of LPS induced chronic and relatively mild ISS. Repeated injection with increasing amounts of LPS is a suitable model for studying nutrient metabolism and evaluating the efficacy of nutritional intervention during chronic ISS in growing pigs.     

PYY(3-36) reduces food intake and body weight and improves insulin sensitivity in rodent models of diet-induced obesity

The gut hormone peptide YY (PYY) was recently proposed to comprise an endogenous satiety factor. We have studied acute anorectic functions of PYY(3-36) in mice and rats, as well as metabolic effects of chronic PYY(3-36) administration to diet-induced obese (DIO) mice and rats. A single intraperitoneal injection of PYY(3-36) inhibited food intake in mice, but not in rats. We next investigated the effects of increasing doses (100, 300, and 1,000 microg.kg-1.day-1) of PYY(3-36) administered subcutaneously via osmotic minipumps on food intake and body weight in DIO C57BL/6J mice. Whereas only the highest dose (1,000 microg.kg-1.day-1) of PYY(3-36) significantly reduced food intake over the first 3 days, body weight gain was dose dependently reduced, and on day 28 the group treated with 1,000 microg.kg-1.day-1 PYY(3-36) weighed approximately 10% less than the vehicle-treated group. Mesenteric, epididymal, retroperitoneal, and inguinal fat pad weight was dose dependently reduced. Subcutaneous administration of PYY(3-36) (250 and 1,000 microg.kg-1.day-1) for 28 days reduced body weight and improved glycemic control in glucose-intolerant DIO rats. Neither 250 nor 1,000 microg/kg PYY(3-36) elicited a conditioned taste aversion in male rats.     

The effect of the glucocorticoid Oradexon on endotoxin-induced peritoneal cell response

Glucocorticoids are important modulators of immune reactions. They are capable of antagonising several effects of the bacterial endotoxin by inhibiting endotoxin-induced leukocyte activation, and the production of cytokines and inflammatory mediators. We earlier demonstrated that the antiglucocorticoid RU 38486 enhances the cytokine production induced by endotoxin and aggravates the course of experimental endotoxic and septic shock. In the present study we investigated the effect of the glucocorticoid Oradexon on the endotoxin-induced peritoneal cell response. For measurement of the peritoneal cell response, male CFLP mice (20-25 g) were injected i.p. with 10 microg/10 g body weight endotoxin (E. coli 026:B6 LPS, Difco Lab, Detroit, lot 110273JB). Dexamethasone (Oradexon, N.V, Organon Oss, The Netherlands) was administered i.p., i.v. or s.c. in a dose of 0.1 mg/10 g body weight, alone or concomitantly with endotoxin. We found that bacterial endotoxin increased the total cell count due to neutrophilia at 24 hours and, due to increases in the number of macrophages and lymphocytes 48 and 72 hours after treatment, respectively. The i.p., i.v., and s.c. injection of Oradexon, increased the total cell count and the macrophage count at 24, 48 and 72 hours. The i.p., s.c. and i.v. injection of Oradexon, concomitantly with endotoxin, reduced the total cell count at 48 and 72 hours, due to decreases in the macrophage count. The i.p., i.v. or s.c. administration of Oradexon concomitantly with LPS decreased the lymphocyte count and the neutrophil count at 24 and 72 hours. These results prove that glucocorticoids are capable of modifying the immune cell reactions induced by endotoxin.