Cortisone-sensitive, innate resistance to Hymenolepis nana infection in congenitally athymic nude rats

The innate resistance of the unnatural rat host to the mouse tapeworm Hymenolepis nana is cortisone sensitive but thymus independent. When congenitally athymic nude rats were orally given eggs, cysticercoids, or adult worms of H. nana, no lumenal adults were established except when they were treated with cortisone acetate during the expected lumenal development. The effect of cortisone to promote adult maturation in the rats was compared in nude and normal rats given eggs of H. nana. The fecundity of the worms (assessed by the fresh worm biomass and the number of infective eggs produced) was much higher in cortisone-treated nude rats than in cortisone-treated normal rats. When the nude rats reconstituted with thymocytes were given eggs and treated with cortisone, the fecundity of H. nana dropped to the same level as in cortisone-treated normal rats. It is strongly suggested that the unnatural rat host has thymus-independent cortisone sensitive resistance to an initial infection (which is the main component of the innate resistance and blocks the lumenal establishment of this parasite) and thymus-dependent resistance (which suppresses the established worms' fecundity and may be ascribed to acquired resistance to the ongoing infection).     

Effect of substrate and small doses of cortisone on the induction of Tryptophan 2,3-dioxygenase (author's transl)]

A number of enzymes are induced by steroid hormones. In this paper the reaction of tryptophan 2,3-dioxygenase is further analyzed. In particular we show in which way the substrate and low doses of cortisone cause an induction. 1) For the induction of tryptophan 2,3-dioxygenase in adrenalectomized rats by 2.5 mg cortisone/kg, the presence of the substrate is necessary as well. Under these conditions an induction of the enzyme can already be registered in the presence of 12.5 mg L-tryptophan/kg. 2) In animals treated before with cortisone, the enzyme maximum appears 30 min after L-tryptophan injection, The enhancement of enzyme activity in animals which are treated with 2.5 mg cortisone/kg before is blocked by actidione only until 30 min after L-tryptophan injection. 3) Experiments with antibodies in animals treated with a low dosis of cortisone show that L-tryptophan acts mainly via enzyme degradation or the saturation with the coenzyme hematin, respectively.     

5'-AMP hydrolysis by suspensions and homogenates of pancreatic islet cells from normal and cortisone-treated rats.

Suspensions of endocrine pancreas cells were prepared by shaking collagenase-isolated rat islets of Langerhans in calcium-free buffer. When incubated with 1.0 mM substrate at pH 7.4, the cells split Pi from 5'-AMP at a rate of 87 nmol/h per microgram DNA, and from beta-glycerophosphate at a rate of 25 nmol/h per microgram DNA. Km for 5'-AMP was about 54 microM. Adenosine or theophylline inhibited the 5'-AMP hydrolysis. Homogenization of the cells increased the activity toward 5'-AMP by 23% and that toward beta-glycerophosphate by 115%. Injecting rats with cortisone had no effect on the 5'-AMP hydrolysis by whole cells but significantly increased the activity in cell homogenates; the intracellular activity toward 5'-AMP was more than doubled by the cortisone treatment. Staining whole islet cells for 5'-AMP-splitting activity resulted in a demarcation of the cell periphery in control rats. Cells from cortisone-treated rats showed heavier deposits of reaction product, and their cell periphery did not stand out as clearly. It is suggested that 5'-nucleotidase is largely an ectoenzyme in normal rat islet cells. The cells also contain an as yet unidentified intracellular phosphatase that seems to be solely responsible for the increased hydrolysis of 5'-AMP in cortisone-treated rats.     

Comparison of inhibition by a tumor promoter (12-O-tetradecanoylphorbol-13-acetate) of expression of the differentiated phenotype of chondrocytes in rabbit costal chondrocytes in culture with inhibition by retinoic acid

Both retinoids and the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) inhibit expression of the differentiated phenotype by rabbit costal chondrocytes in culture, as judged by morphological changes and decreased sulfation of glycosaminoglycans (GAG). However, the inhibition of the differentiated phenotype of chondrocytes in TPA-treated cells is restored by parathyroid hormone (PTH), while the inhibition by retinoids is not [Takigawa et al. (1982) Mol. Cell. Biochem. 42, 145-153; Takigawa et al. (1983) Cell Differ. 13, 283-291]. In the present study, we examined the difference between TPA-treated chondrocytes and retinoic acid-treated chondrocytes to determine the mechanism of the restoration of the differentiated phenotype in de-differentiated cells treated with TPA. PTH increased the activity of ornithine decarboxylase [ODC; EC 4.1.1.17], a rate limiting enzyme of polyamine biosynthesis, and proteoglycan synthesis in chondrocytes pretreated with TPA as well as in normal chondrocytes. The maximal stimulations of ODC activity and GAG synthesis were observed 4 h and 24-36 h, respectively, after addition of PTH. The dose-response curve for ODC induction by PTH was parallel to that of PTH-stimulated proteoglycan synthesis both in TPA-treated chondrocytes and in normal chondrocytes. PTH also increased the intracellular cyclic AMP level after 2 min in TPA-treated cells as in normal cells. Addition of dibutyryl cyclic AMP (DBcAMP) induced ODC and restored proteoglycan synthesis in TPA-treated cells. The dose-response curve for induction of ODC by DBcAMP was parallel to that of DBcAMP-stimulated proteoglycan synthesis in both TPA-treated chondrocytes and normal chondrocytes. On the other hand, the increases by PTH in the intracellular cyclic AMP level, ODC activity, and proteoglycan synthesis were inhibited in chondrocytes pretreated with a combination of TPA and retinoic acid as well as in those pretreated with retinoic acid alone. TPA stimulated the syntheses of DNA and RNA in chondrocytes but did not increase the cyclic AMP level or ODC activity. PTH and DBcAMP inhibited the syntheses of DNA and RNA both in TPA-treated cells and in normal cells. These results suggest that ODC induction mediated by elevation of cyclic AMP plays an important role in re-differentiation of de-differentiated cells pretreated with these agents.     

Morphofunctional characteristics of the endocrine cells of the stomach following administration of hydrocortisone and L-thyroxine

Electron microscopy with application of specific fluorescent histochemical reaction of Falck, as well as some methods of impregnation made it possible to indentify enterochromaffin cells in the stomach of hyperthyroid rats and the rats after cortisone injection under the conditions ox hyperfunction of the thyroid gland. After 20 days of L-thyroxin injection, and after 10 days of hydrocortisone injection, preceded by L-thyroxin, the amount of enterochromaffin cells in the epithelial layer of the gastric mucosa were noted to increase that was accompanied by simultaneous increase of the number of secretory argyrophil granules in their cytoplasm. Simultaneous injection of L-thyroxin and hydrocortisone, while not decreasing statistically significant amount of the cells, produced degradation of their cytoplasm.     

Cell migration and cortisone induction of sucrase activity in jejunum and ileum

The increase of sucrase activity in homogenates of jejunum and ileum of suckling rats after cortisone administration has been investigated. Serial tissue sections of villi and crypts were also assayed for sucrase activity and these results were compared with the migration of cells labelled with [(3)H]thymidine along the villus. By using a low dose of cortisone (0.5mg/day per 100g body wt.) it was found that the sensitivity of the small intestine producing system to cortisone stimulation increased during the suckling period. On the other hand, 5mg of cortisone/day per 100g body wt. produced practically the same increase of sucrase during the entire suckling period. Sucrase activity in homogenates of the entire small-intestinal wall was first detected 24h after the first injection of cortisone (5mg/day per 100g body weight) to 9-day-old animals and maximum activity both in the jejunum and ileum was reached by 120h. Jejunal activity was greater than ileal activity, but the rate of the increase was similar. The half-time of the increase was 23-27h, whereas enterocytes migrate from the base to the tip of the villi in approximately 72h. Comparison of sucrase activity in serial tissue sections of villi and crypts at various times after cortisone treatment showed that the leading edge of sucrase activity proceeds toward the tip of the villi at the same rate as the advancing edge of newly formed cells. Sucrase activity increased in the newly induced cells as they migrated to the tip of the villi. It was concluded that the increase of sucrase activity in suckling rats after cortisone stimulation is due to at least three factors: (1) increase of activity in newly differentiating cells, (2) increased percentage of villus cells with sucrase activity and (3) continued production or activation of sucrase activity as the cells migrate along the villi.     

Plasminogen activator production in a rat model of Pneumocystis carinii pneumonia

Several studies have indicated that the serine protease urokinase-plasminogen-activator (uPA) is an important factor in host defense against pulmonary pathogens. To gain a better insight into the role of uPA in Pneumocystis carinii (P. carinii) pneumonia (PCP), we evaluated PA production in alveolar macrophages (AMs) obtained from rats with steroid-induced PCP. Treatment with cortisone acetate favored PCP in 91% of rats. In the bronchoalveolar lavage (BAL) samples of immunosuppressed rats both with and without PCP, we observed a decrease in uPA activity as well as a decrease in cell number. Urokinase-PA production by AMs was reduced in rats treated with cortisone alone. However, an increase in cell-associated uPA was observed in rats with PCP. This increase appears to be produced in response to P carinii infection. In fact, when AMs obtained from untreated healthy or immunosuppressed uninfected rats were challenged with P carinii, a significant increase in PA activity in cell lysates was observed, though a lower response was obtained in cortisone-treated animals. Our results suggest that healthy AMs respond to the presence of P carinii with an increase in uPA production and that this response in immunodepressed rat-AMs is partially impaired.     

Norepinephrine interference in adrenal hormone balance related to blood calcium effects of PTH (author's transl)]

Decreased hypercalcemic effects of PTH are observed after medulloadrenalectomy, (table I), metoprione (table II) or cortisone (table IV) treatments in guinea pigs. 2. Norepinephrine restores the blood calcium effects of PTH in these cases but epinephrine is inactive. 3. Immediate activation of kidney adenylate cyclase by PTH (increased urinary AMPc) is also reduced in medulloadrenalectomised, cortisone or metopirone treated guinea pigs (table V). But in this test, norepinephrine reduces the effect of PTH (fig. 1).     

Thyroid C cells of middle-aged rats treated with estradiol or calcium

 The structure and function of C cells of middle-aged female rats (14-months old) treated with estradiol dipropionate (EDP), calcium (Ca) or a combination of EDP+Ca were studied. A stereological method was used to determine the volume of calcitonin (CT)-immunoreactive C cells and their nuclei, and the relative volume density and mean number of the C cells per section were calculated. Serum levels of CT, osteocalcin, parathyroid hormone (PTH), and β-estradiol were also measured. A significant decrease in body weight of the rats treated with EDP or EDP+Ca was observed. These treatments led to a significant decrease in cellular and nuclear volumes, relative volume density, and mean number of C cells per section, in comparison with the corresponding controls. A reduction of the serum level of CT, PTH, and osteocalcin was also recorded in EDP- and EDP+Ca-treated animals. No statistically significant differences between Ca- and vehicle-injected rats, with regard to all morphometric C cell parameters and biochemical values determined, were seen. However, a conspicuous degranulation of the C cells and decreased immunoreactivity for CT in the Ca-receiving group, which could be interpreted as the signs of increased activity of these cells, were noticed. This effect of Ca was also observed in rats injected with EDP and Ca in combination, when the inhibitory effect of EDP on C cell function was less noticeable than in the group treated with EDP alone. Accepted: 29 July 1997     

The effects of aluminum loading on the renal response to parathyroid hormone in the vitamin D-replete rat

Aluminum (Al) may cause vitamin D-resistant osteomalacia and depress the serum levels of immunoreactive parathyroid hormone (iPTH) in patients treated with maintenance dialysis and those on total parental nutrition (TPN). Both conditions have been associated with low serum levels of 1,25(OH)2-vitamin D (1,25(OH)2D). Al may inhibit PTH secretion in vitro; however, induction of hypocalcemia can enhance endogenous PTH secretion in Al-loaded dogs and TPN patients. Despite hypocalcemia and/or increased endogenous iPTH levels, Al-loaded TPN patients fail to show the expected rise in serum 1,25(OH)2D levels. Such observations suggest that Al may impair the renal response to PTH. We studied vitamin D-replete rats given Al or saline vehicle IP for 5 days. Al and control rats then received a saline infusion with an IV bolus of PTH 1-34. Urinary cyclic AMP and P excretion rose in Al and control rats by 1 hr post-PTH, without differences between the groups. Serum P and ionized Ca levels were not different between Al and control rats. In other Al and control rats, serum 1,25(OH)2D levels were measured after saline without PTH. Serum 1,25(OH)2D levels were higher in controls given PTH than in those without, but 1,25(OH)2D levels were not different between Al rats given PTH and those with none. Thus, aluminum does not affect cyclic AMP or P excretion but may impair 25(OH)D-1 alpha-hydroxylase activity in response to PTH.     

Development of the small intestine in the hypophysectomized rat. II. Influence of cortisone, thyroxine, growth hormone, and prolactin.

The intestinal deficiencies caused by hypophysectomy of rats at 6 days of age can be repaired to varying degrees by thyroxine or cortisone but not by growth hormone or prolactin. Administration of daily doses of thyroxine alone from 19–22 days raises duodenal alkaline phosphatase activity to normal levels at 24 days; it has a strong effect on jejunal sucrase and maltase, although these activities remain below those of controls. Thyroxine causes a marked increase in rough endoplasmic reticulum and restores the Golgi complexes to their normal appearance. It also elicits an intensification of periodic acid-Schiff (PAS) stainability of the brush border. Cortisone acetate given from 19 to 22 days elevates sucrase and maltase to normal levels but does not fully restore phosphatase activity. Like thyroxine, cortisone causes intensification of PAS staining of the brush border and also increases rough endoplasmic reticulum. It seems to stimulate Golgi activity, but results in the appearance of a variety of abnormal forms. The defects in Golgi configuration, brush border carbohydrate content, and activity of glycoprotein enzymes that are bound to the brush border may all reflect impaired glycosylation in the hypophyseoprivic state; the results of thyroxine or cortisone administration suggest that both hormones may affect glycosylation but in different ways.     

Effects of parathyroid hormone on plasma zinc concentration in rat with chronic renal failure

Although both secondary hyperparathyroidism (HPT) and hypozincemia are commonly observed in humans and animals with chronic renal failure (CRF), the relationship between secondary HPT and hypozincemia is little delineated. The present study was designed to examine whether the elevated plasma parathyroid hormones (PTH) levels do affect the disposition of extrarenal zinc and decrease plasma zinc level in CRF rats. The experiment was performed in normal and CRF rats with intact parathyroid gland and parathyroidectomized (PTX), using an acute zinc load alone or in combination with PTH infusion in five groups of rats: normal control, CRF control, CRF + PTH, CRF + PTX and CRF + PTX + PTH. Five sixths nephrectomy was used to produce CRF. All rats were infused with 0.05 mg/kg/min ZnSO4 alone or in combination with 10 microg/kg/min PTH through intravenous infusion for 90 min with serial monitoring of plasma zinc levels every 30 min. The alteration of plasma interleukin-6 (IL-6) levels and the effect of zinc levels in red blood cells (RBCs), as well as the output of bile juice zinc and urinary zinc excretion during the 90-min infusion were also examined. After 90-min infusion, liver tissue was harvested to determine its contents of zinc and metallothionein (MT). During zinc sulfate infusion, the responses of plasma zinc concentration in PTH-combined infusion groups markedly decreased as compared with those of the non-PTH-combined infusion groups, especially in the CRF rats with PTX. However, when zinc sulfate alone was infused, the response of plasma zinc concentration was found to increase in CRF rats with PTX as compared with that of the CRF control rats. PTH infusion groups significantly increased the levels of plasma IL-6 (P < 0.05), but it did not alter the levels of RBC zinc and the secretion of bile zinc during the 90-min infusion. After 90-min zinc sulfate infusion, higher liver zinc and MT contents were found in CRF control, CRF + PTH and CRF + PTX + PTH rats, but were [corrected] not found in the CRF + PTX rats. Zinc sulfate infused alone was found to increase the excretion of basal zinc in bile juice and urine, in both normal and CRF rats. The percentage of zinc load translocated out from the plasma during 90-min zinc sulfate infusion significantly rises in CRF rats and CRF rats with PTH-combined infusion as compared with normal control rats. However, in CRF rats with PTX, the percentage of zinc load translocated out from plasma during 90-min zinc sulfate infusion was similar to that in the normal control rats. Therefore, we suggested that in CRF rats, the excessive secretion of PTH may play a role in the pathogenesis of hypozincemia because PTH enhanced extrarenal zinc disposal.     

Diaphragm atrophy and weakness in cortisone-treated rats

Despite frequent therapeutic use, the potential of corticosteroids to produce respiratory muscle myopathy is unknown. We studied effects of chronic steroid treatment on diaphragm mass and function. Eleven Sprague-Dawley rats were treated with cortisone acetate (100 mg.kg-1.day-1 im) for 10 days. Controls (injected with vehicle) included 11 freely eating rats and 11 animals pair fed to match food intake of cortisone rats. Steroid treatment depressed body weight 30% compared with controls. Mass of diaphragm, gastrocnemius, and extensor digitorum longus showed significant atrophy (30%); heart and soleus were unaffected. Isometric contractile properties of costal diaphragm strips were studied in vitro using direct stimulation. The force-frequency relationship was markedly depressed by steroid treatment, both at low and high frequencies. However, force developed per unit cross-sectional area was similar among all three groups, as were twitch characteristics. When stimulated every minute, forces developed by control strips fell progressively, whereas the forces of cortisone-treated strips remained unchanged. When stimulated every 5 s, the fall in force was not different between groups. We conclude that cortisone weakened the diaphragm by decreasing muscle mass but made the diaphragm more resistant to one form of fatigue in vitro.     

Plasminogen activator regulation in osteoblasts: parathyroid hormone inhibition of type-1 plasminogen activator inhibitor and its mRNA.

In order to determine the mechanism by which parathyroid hormone (PTH) stimulates plasminogen activator (PA) activity in rat osteoblasts, we investigated the effect of human PTH(1-34) [hPTH(1-34)] on the synthesis of mRNAs for tissue-type PA (tPA), urokinase-type PA (uPA), and PA inhibitor-1 (PAI-1), and on release of PA activity and PAI-1 protein in both normal rat calvarial osteoblasts and UMR 106-01 osteogenic sarcoma cells. hPTH(1-34) (0.25-25 nM) decreased PAI-1 mRNA and protein, and increased PA activity in both cell types in a dose-dependent manner with ED50 of about 1 nM for both responses. Forskolin and isobutylmethylxanthine also stimulated PA activity and decreased PAI-1 protein and mRNA in both cell types. hPTH(1-34) did not show any consistent effect on tPA and uPA mRNA in calvarial osteoblasts, but a modest (two-fold) increase of both mRNAs was observed in UMR 106-01 cells treated with 25 nM hPTH(1-34). However, when protein synthesis was inhibited with 100 microM cycloheximide, the increase of tPA and uPA mRNA by hPTH(1-34) was enhanced in UMR 106-01 cells and became evident in calvarial osteoblasts. Fibrin autography also revealed that hPTH(1-34) increases tPA and uPA activity, especially after cycloheximide treatment in UMR 106-01 cells. These results strongly suggest that PTH increases PA activity predominantly by decreasing PAI-1 protein production through a cyclic adenosine monophosphate (cAMP)-dependent mechanism in rat osteoblasts. The reduction of PAI-1 protein by PTH results in enhanced action of both tPA and uPA, and would contribute to the specific roles of these PAs in bone.     

Hymenolepis nana: worm recovery from congenitally athymic nude and phenotypically normal rats and mice

When eggs or mouse-derived cysticercoids of Hymenolepis nana were inoculated into previously uninfected congenitally athymic nude (rnu/rnu) rats of an outbred Rowett strain, they failed to mature in the intestinal lumen. They also failed to mature in phenotypically normal (rnu/+) littermates, except when these hosts were treated with cortisone acetate from the beginning of the lumen phase. The Rowett rat, either thymus-deficient or not, was susceptible to tissue cysticercoids but resistant to luminal adults. It is therefore considered to be an unnatural host, at least for mouse-derived H. nana. There was little or no difference in susceptibility to initial tissue cysticercoids between these nude rats and phenotypically normal ones. The normal rats became completely resistant to reinfection with eggs and no secondary cysticercoids developed in their intestinal tissue, whereas the nude rats showed unaltered susceptibility to secondary tissue cysticercoids. Thus, acquired resistance to egg challenge, assessed by the failure of tissue cysticercoid recovery, was thymus-dependent. However, innate resistance to both a primary egg dose, assessed by the low recovery rates of tissue cysticercoids, and to a primary cysticercoid dose, assessed by the failure of luminal adult recovery, were thymus-independent. The effect of cortisone acetate to initiate maturation of H. nana appeared to be unrelated to thymus function. In contrast, all mice, either thymus-deficient or not, were highly susceptible to both phases. The number of worms recovered was more than 10 times greater than that of cysticercoids established in the rat's intestinal tissue.(ABSTRACT TRUNCATED AT 250 WORDS)     

Light- and electron microscopic observations on parathyroid glands in different age groups of rats

The parathyroid hormone (PTH) acts on bones, intestines, and kidneys to maintain the calcium homeostasis which, in turn, is a main factor in controling the parathyroid (PT) gland activity. In all mammals studied, the chief cells of PT glands changed their size, shape, and cytoplasmic structure due to different functional states which vary the serum calcium levels. The chief cells of the rat PT glands were classified as dark and light. The dark cells may constitute an active form, characterized mainly by the abundant free ribosomes, conspicuous rough endoplasmic reticulum, and GOLGI complexes, greater number of secretory granules (SG) and increased tortuosity of the plasma membranes as compared to the light ones which were considered as a less active type of cells. Due to different calcium requirements in newborn and young rats for the ossification of growing skeleton and in adult and senile rats with consolidate mature bones, the PT glands studied with electron microscope showed various cytological features. The parenchyma of newborn and young PT glands was composed by dark chief cells. The light chief cells were more frequent in adult and senile animals as a less active type of cell. Mature SG were only occasionally observed in dark cells of newborn, young and adult PT glands. They may constitute a reserve supply of PTH but probably not the main way of secretion, according to their little number. Another pool of PTH probably answers the needs for the small basal variations in the steady-state secretion and may be represented by the vesicles observed in the chief cells cytoplasm.     

T cells potentiate PTH-induced cortical bone loss through CD40L signaling

Parathyroid hormone (PTH) promotes bone catabolism by targeting bone marrow (BM) stromal cells (SCs) and their osteoblastic progeny. Here we show that a continuous infusion of PTH that mimics hyperparathyroidism fails to induce osteoclast formation, bone resorption, and cortical bone loss in mice lacking T cells. T cells provide proliferative and survival cues to SCs and sensitize SCs to PTH through CD40 ligand (CD40L), a surface molecule of activated T cells that induces CD40 signaling in SCs. As a result, deletion of T cells or T cell-expressed CD40L blunts the bone catabolic activity of PTH by decreasing bone marrow SC number, the receptor activator of nuclear factor-κB ligand (RANKL)/OSTEOPROTEGERN (OPG) ratio, and osteoclastogenic activity. Therefore, T cells play an essential permissive role in hyperparathyroidism as they influence SC proliferation, life span, and function through CD40L. T cell-SC crosstalk pathways may thus provide pharmacological targets for PTH-induced bone disease.     

Purification and characteristics of glucocorticoid antagonizing factor in endotoxemia

The present study involved the purification of GAF (glucocorticoid antagonizing factor) released in blood of endotoxemic mice, using the inhibition rate of tryptophan oxygenase (TO) activity in the mice liver as a parameter, to determine if this plays a role in metabolic disorders. GAF-rich serum in zymosan-primed and endotoxin-injected mice was subjected to chromatography on DEAE-Sepharose CL-6B, Blue Sepharose CL-6B and Sephadex G-200 superfine columns. Finally, GAF fractions were purified by chromatography on a DEAE-Sepharose CL-6B column. The purified GAF showed a single band in electrophoresis in sodium dodecyl sulfate (SDS) polyacrylamide gel. The molecular weight of GAF was estimated to be 90,000. The purified GAF was regarded as glycoprotein. No factor (100 micrograms) exhibited lethal action on mice. The activity of TO in cortisone treated mice after injection of purified GAF was markedly lower than that in cortisone alone treated mice. On the other hand, there were no differences in tyrosine aminotransferase activities between the GAF plus cortisone injected group and cortisone only treated group. The glucose level after injection of GAF in cortisone treated mice initially showed hyperglycemia, but declined toward hypoglycemia 2 hr after injection, and thereafter returned nearly to the normal range by 4 hr. The liver glycogen level in GAF plus cortisone-treated mice was markedly lower than that in cortisone-alone treated mice.     

Effects of deflazacort and cortisone on cellular proliferation in the rat thymus

Deflazacort is a relatively new glucocorticoid with significant immunosuppressant activity and presumably fewer side effects. The present study was designed to compare the effects of deflazacort on the proliferative activity of thymus cells and thymolysis with the growth inhibition. We treated Long-Evans rats for nine days with cortisone (CORT, 5.0 mg/day), deflazacort (DFZ, 0.15 mg/day), and control vehicle (CTRL). Animals were sacrificed 1 hour after injection of bromodeoxyuridine (BrdUrd) on day 10. BrdUrd-labeled thymic cells were quantified without knowledge of treatment. A Labeling Index (LI), expressed as the number of BrdUrd BrdUrd-labeled cells per 100 total cells and the Numerical Density (ND), expressed as the total number of cells per 100 microm(2) were calculated. Treatment with either glucocorticoid resulted in a significant and equal decrease of thymus weight, indicating a marked reduction in total immunogenic tissue. A general alteration of thymic histological structure occurred in the CORT group. The LI was not different between CTRL and DFZ groups, 6.9 and 7.9% of cells were labeled respectively. In the CORT group, the LI was 2.5%. With respect to Numerical Density, the CTRL group had the greatest value (14.6 +/- 0.4 cells/100 microm(2)), with the DFZ (12.3 +/- 0.06 cells/100 microm(2)) and CORT groups being significantly lower (10.4 +/- 0.5 cells/100 microm(2)). Although regression analysis of thymus weight pointed to bioequivalence of the glucocorticoid dosages used, BrdUrd-labeling raised the possibility that the cells still present in the thymus of DFZ-treated animals retained, at least partially, their normal capacities for proliferation.