ABSTRACT
In a serum-free medium addition of insulin-like growth factor-1 (IGF-1) consistently enhanced lymphocyte proliferation response to PHA in a dose-dependent fashion. This effect was produced by an acceleration in the expression of clone expansion and not in the number of proliferating cells. This was documented by kinetics data obtained from the first proliferation round of PHA-stimulated lymphocytes, in which addition of IGF-1 reduced G1-phase length, without changing G0-phase, S-phase or cloned size. The data were confirmed in 10-day culture of stimulated lymphocytes where IGF-1 only accelerated cell proliferation without modifying the area enclosed by the proliferation curve. As IGF-1 is under the control of growth hormone, our results suggest that some of the immuno-regulation effects ascribed to growth hormone in vivo could be produced by IGF-1.
Subject(s)
Insulin-Like Growth Factor I/pharmacology , Lymphocyte Activation/drug effects , Cell Cycle/drug effects , Cells, Cultured , Culture Media, Serum-Free/pharmacology , DNA Replication/drug effects , Humans , Phytohemagglutinins/pharmacology , Stimulation, ChemicalABSTRACT
We have compared the immunosuppressive effect of delta HOP and glucocorticoids on lymphocyte proliferation and IL-1 secretion. The new synthetic steroid only inhibited proliferation of phytohaemagglutinin (PHA)-stimulated human lymphocyte at high concentrations and the effect did not persist after washing out the steroid. In contrast, glucocorticoids produced the classical dose-response inhibition and the effect persisted when they were removed from the cultured medium. Although both steroids decreased IL-1 secretion from human monocytes stimulated with lipopolysaccharide (LPS), they exert the same effect through a different mechanism. The experiments we report suggest that the decrease of IL-1 synthesis produced by delta HOP could be caused by inhibition of LPS phagocytosis. These results support our hypothesis that delta HOP exerts its immunosuppressive and anti-inflammatory effect by a non-genomic mechanism.
Subject(s)
Hydroxyprogesterones/pharmacology , Lymphocyte Activation/drug effects , Adult , Animals , Candida albicans/immunology , Glucocorticoids/pharmacology , Humans , Immunosuppressive Agents , In Vitro Techniques , Interleukin-1/metabolism , Macrophages/immunology , Phagocytosis/drug effects , RatsABSTRACT
The effect of delta HOP on the formation of concanavalin A (Con A) caps and steady state anisotropy (rs) obtained in 1,6-diphenyl-1,3,5-hexatriene (DPH) labeled thymocyte plasma membranes was compared with the effect of glucocorticoids on these experiments. Results demonstrate that delta HOP decreased cap formation "in vivo" as well as "in vitro" and that it did not change fluorescence anisotropy "in vitro". Glucocorticoids had an opposite effect, increasing fluidity apparently through a glucocorticoid specific mechanism not exerted by delta HOP.
Subject(s)
Cell Membrane Permeability/drug effects , Hydroxyprogesterones/pharmacology , Receptors, Concanavalin A/physiology , Thymus Gland/cytology , Animals , Fluorescence Polarization , Male , Membrane Fluidity/drug effects , Rats , Rats, Inbred Strains , Receptor AggregationABSTRACT
The effect of delta HOP on the formation of concanavalin A (Con A) caps and steady state anisotropy (rs) obtained in 1,6-diphenyl-1,3,5-hexatriene (DPH) labeled thymocyte plasma membranes was compared with the effect of glucocorticoids on these experiments. Results demonstrate that delta HOP decreased cap formation [quot ]in vivo[quot ] as well as [quot ]in vitro[quot ] and that it did not change fluorescence anisotropy [quot ]in vitro[quot ]. Glucocorticoids had an opposite effect, increasing fluidity apparently through a glucocorticoid specific mechanism not exerted by delta HOP.
ABSTRACT
The effect "in vivo" of 11 beta-hydroxy-pregna-1,4-diene-3,20-dione (delta HOP) in acute and chronic treatment was studied in mice compared to those treated with dexamethasone and vehicle. In acute experiments an injection of 2 mg/100 g body weight of delta HOP had a maximal inhibitory effect in 3H-uridine incorporation by thymocytes 18 h after the injection, disappearing 36 h later, meanwhile no change was observed in plasma corticosterone levels at any time. The dose 0.033 mg/100 g body weight of dexamethasone produced a high inhibition 5 h after the injection, and a significant decrease in plasma corticosterone was produced at this time; the effect disappeared at 24 h. In the chronic treatment delta HOP produced the maximal inhibition 5 h after the treatment; this effect was maintained until 36 h and disappeared at 48 h without change in corticosterone levels. Meanwhile dexamethasone produced the same inhibition as delta HOP 5 h after the treatment; this effect disappeared after 18 h. In those animals plasma corticosterone decreased during longer time than in acute treatment, since it continued lower than normal at 18 h and it recovered at 24 h. After 5 h of a chronic treatment delta HOP did not change thymus and spleen weights, but they decreased with dexamethasone treatment. These results suggest that the "in vivo" actions of delta HOP is different from that of glucocorticoids.
Subject(s)
Corticosterone/blood , Dexamethasone/pharmacology , Hydroxyprogesterones/pharmacology , Thymus Gland/cytology , Tritium/metabolism , Uridine/metabolism , Animals , Dexamethasone/administration & dosage , Female , Hydroxyprogesterones/administration & dosage , Male , Mice , Mice, Inbred BALB CABSTRACT
The effect [quot ]in vivo[quot ] of 11 beta-hydroxy-pregna-1,4-diene-3,20-dione (delta HOP) in acute and chronic treatment was studied in mice compared to those treated with dexamethasone and vehicle. In acute experiments an injection of 2 mg/100 g body weight of delta HOP had a maximal inhibitory effect in 3H-uridine incorporation by thymocytes 18 h after the injection, disappearing 36 h later, meanwhile no change was observed in plasma corticosterone levels at any time. The dose 0.033 mg/100 g body weight of dexamethasone produced a high inhibition 5 h after the injection, and a significant decrease in plasma corticosterone was produced at this time; the effect disappeared at 24 h. In the chronic treatment delta HOP produced the maximal inhibition 5 h after the treatment; this effect was maintained until 36 h and disappeared at 48 h without change in corticosterone levels. Meanwhile dexamethasone produced the same inhibition as delta HOP 5 h after the treatment; this effect disappeared after 18 h. In those animals plasma corticosterone decreased during longer time than in acute treatment, since it continued lower than normal at 18 h and it recovered at 24 h. After 5 h of a chronic treatment delta HOP did not change thymus and spleen weights, but they decreased with dexamethasone treatment. These results suggest that the [quot ]in vivo[quot ] actions of delta HOP is different from that of glucocorticoids.
ABSTRACT
The effect [quot ]in vivo[quot ] of 11 beta-hydroxy-pregna-1,4-diene-3,20-dione (delta HOP) in acute and chronic treatment was studied in mice compared to those treated with dexamethasone and vehicle. In acute experiments an injection of 2 mg/100 g body weight of delta HOP had a maximal inhibitory effect in 3H-uridine incorporation by thymocytes 18 h after the injection, disappearing 36 h later, meanwhile no change was observed in plasma corticosterone levels at any time. The dose 0.033 mg/100 g body weight of dexamethasone produced a high inhibition 5 h after the injection, and a significant decrease in plasma corticosterone was produced at this time; the effect disappeared at 24 h. In the chronic treatment delta HOP produced the maximal inhibition 5 h after the treatment; this effect was maintained until 36 h and disappeared at 48 h without change in corticosterone levels. Meanwhile dexamethasone produced the same inhibition as delta HOP 5 h after the treatment; this effect disappeared after 18 h. In those animals plasma corticosterone decreased during longer time than in acute treatment, since it continued lower than normal at 18 h and it recovered at 24 h. After 5 h of a chronic treatment delta HOP did not change thymus and spleen weights, but they decreased with dexamethasone treatment. These results suggest that the [quot ]in vivo[quot ] actions of delta HOP is different from that of glucocorticoids.
ABSTRACT
The strong inhibition of thymocyte-RNA synthesis by 11 beta-hydroxypregna-1, 4-diene-3, 20-dione (delta HOP) reported recently, fulfills the three conditions required for a non-genomic effect, i.e.: no persistence upon washing out, instantaneous action and effect in the presence of inhibitors of RNA synthesis. Injection of (delta HOP) into mice (2 mg/100 g) also causes a 32% inhibition in their thymocyte-RNA synthesis, but the mechanism of this latter inhibition has still not been clarified.
Subject(s)
Hydroxyprogesterones/pharmacology , RNA/biosynthesis , Thymus Gland/cytology , Uridine/metabolism , Animals , Culture Media , Mice , Mice, Inbred BALB C , Protein Biosynthesis , Rats , Rats, Inbred Strains , Thymus Gland/metabolismABSTRACT
The strong inhibition of thymocyte-RNA synthesis by 11 beta-hydroxypregna-1, 4-diene-3, 20-dione (delta HOP) reported recently, fulfills the three conditions required for a non-genomic effect, i.e.: no persistence upon washing out, instantaneous action and effect in the presence of inhibitors of RNA synthesis. Injection of (delta HOP) into mice (2 mg/100 g) also causes a 32
inhibition in their thymocyte-RNA synthesis, but the mechanism of this latter inhibition has still not been clarified.