Biomedical subjects

T Geiger

Publications and source records attributed to T Geiger.

At least 37 records · Page 2Linked to original sources

PubMed1994

CGP 47969A: effect on collagen induced arthritis in DBA/1 mice.

OBJECTIVE: CGP 47969A is a novel and potent inhibitor of cytokine biosynthesis in human and murine monocytic cells. The effect of CGP 47969A on collagen induced arthritis (CIA) in DBA/1 mice was investigated and compared to that of prednisolone. METHODS: CIA was induced by intradermal injection of type II collagen in CFA at Day 0. CGP 47969A was applied orally, 5 times/week, starting at Day 15 after immunization. Arthritic signs were recorded 3 times/week for clinical scoring and radiographic analysis was performed at the end of the experiment at Day 60. Serum amyloid P (SAP) and anticollagen antibody titers were determined by ELISA at Day 60. RESULTS: CGP 47969A dose dependently reduced the incidence of arthritis from 93% in the positive control group to 60, 40, 30 and 10% at doses of 1, 5, 25 and 60 mg/kg/day, respectively. At a dose of 120 mg/kg, CGP 47969A totally prevented the occurrence of arthritis (ED50 between 1 and 5 mg/kg). Prednisolone at 3 and 30 mg/kg reduced the arthritis incidence to 70 and 30%, respectively. CGP 47969A dose dependently inhibited the joint destruction, as measured by radiographic scoring and its potency was comparable to that of prednisolone. The elevated serum levels of the positive acute phase protein SAP in arthritic animals were completely normalized by CGP 47969A at a dose of 60 mg/kg, however, neither CGP 47969A nor prednisolone influenced the plasma levels of anticollagen antibodies (IgG). CONCLUSION: Our results demonstrate that CGP 47969A is highly effective in CIA with a potency comparable to that of prednisolone. These promising results justify the expectation that this novel antiarthritic compound now under development might also be effective in the treatment of rheumatoid arthritis in man.

Acute Disease↗

PubMed1993

T cells are responsive to the simian virus 40 large tumor antigen transgenically expressed in pancreatic islets.

The qualities of a peripheral Ag that determine whether T cells will be tolerant of or responsive to it are poorly understood. To approach this problem, we studied the T cell response in a line of transgenic mice selectively expressing an oncoprotein in the islets of Langerhans. The SV40 large tumor Ag (SV40-T) is directed to islet beta-cells in Rip1-Tag3 (RT3) mice by a hybrid insulin promoter-SV40-T construct. Ag is first detected on these cells between 10 and 12 wk after birth. RT3 mice were bred with mice expressing a transgenic rearranged TCR recognizing SV40-T in the context of the class I MHC molecule, H-2Kk. T cell response in the resultant RT3/TCR-double transgenic mice was then analyzed. T cells are fully responsive to SV40-T in RT3/TCR-transgenic mice, and T cells infiltrate the islets of both RT3 and RT3/TCR-transgenic mice. This work demonstrates that T cells may remain responsive to self-Ag expressed outside the thymus, and that this responsiveness may result in autoimmunity. The developmentally delayed expression or the oncogenic nature of SV40-T in the RT3-transgenic mice may be important in determining this T cell response.

Animals↗

PubMed1993

Interferon alpha increases the frequency of interferon gamma-producing human CD4+ T cells.

An increased ratio of T helper type 2 (Th2)- vs Th1-like cells contributes to the immune dysregulation in allergic disease situations and in many chronic infections, including AIDS. Th2-type immune responses are characterized by Th cells that produce increased levels of interleukin-4 (IL-4) and decreased levels of interferon gamma (IFN-gamma). The induction of either a Th1- or a Th2-like phenotype may be critically controlled by the antigen-presenting cells and their cytokines, e.g., IFN-alpha. In this study we have determined the frequencies of potential IL-4- and/or IFN-gamma-producing T cells in the peripheral blood of randomly selected healthy individuals, and analyzed whether IFN-alpha controls IL-4 and/or IFN-gamma production. Purified CD4+ or CD8+ T cells were stimulated for 24 h via the T cell receptor/CD3 complex in the presence or absence of IFN-alpha, and single IL-4- and IFN-gamma-secreting cells were detected in enzyme-linked immunospot assays. In the absence of IFN-alpha, CD4 cells produced IFN-gamma at frequencies of 1:50-300, and produced IL-4 at frequencies of 1:110-<1:100,000. Addition of IFN-alpha during the activation of CD4 cells increased the levels of IFN-gamma mRNA. As a consequence, the numbers of IFN-gamma-producing CD4 cells and the amounts of secreted IFN-gamma increased 10-fold. In contrast, IFN-alpha did not increase the frequency of IL-4-secreting CD4 cells. In the absence of IFN-alpha, addition of exogenous IL-4 to cultures of CD4 cells suppressed IFN-gamma secretion by 70%. However, in the presence of IFN-alpha, IL-4 did not display any suppressive effect. Compared with CD4 cells, CD8 cells produced IFN-gamma more frequently (1:5-10) but IL-4 less frequently (1:5,300 to < 1:100,000). IFN-alpha did not display any effect on the frequency of either IFN-gamma or IL-4 production by CD8 cells. Taken together the results indicate that IFN-alpha increases the frequency of IFN-gamma-secreting CD4 Th cells and antagonizes the suppressive effect of IL-4 on IFN-gamma production. As a consequence, IFN-alpha may favor the induction and maintenance of Th1-like cells and thereby counteract Th2-driven allergic immune responses.

Acquired Immunodeficiency Syndrome↗

PubMed1993

Interleukin-1 (IL-1) production in a mouse tissue chamber model of inflammation. I. Development and initial characterisation of the model.

A simple and reliable animal model to quantify interleukin-1 (IL-1) production at a site of inflammation has been developed and characterised. This model involves the subcutaneous implantation of sterile Teflon chambers (30 mm x 10 mm diameter) into the backs of mice. After 14 days, a straw coloured transudate fluid was present in the lumen of the implanted chamber which was withdrawn for the determination of baseline measurements of various inflammatory parameters. A localised chronic inflammatory response was then induced in the chambers by injection of 1% zymosan or Bordetella pertussis vaccine (BPV) (in presensitised animals). The local inflammatory reaction in the chamber, over a 30 day time course, was characterised by leucocyte infiltration, and marked increases in protein, prostaglandin E2, IL-1 and IL-6 concentrations in the chamber fluid. A rapid increase in plasma concentrations of the acute-phase reactant serum amyloid P (SAP) also occurred. This model allows repeated samples to be obtained from the same animal for the assessment of inflammatory parameters and may be useful for investigating the mechanisms controlling the production of IL-1 during the inflammatory response in vivo.

Animals↗

PubMed1993

Interleukin-1 (IL-1) production in a mouse tissue chamber model of inflammation. II. Identification of (tissue) macrophages as the IL-1 producing cells and the effect of anti-inflammatory drugs.

We have used our newly described mouse tissue chamber model [1], to investigate the process of IL-1 production in more detail. The inflammatory reaction in the tissue surrounding the implanted chambers was investigated histologically and by using the polymerase chain reaction (PCR). The inflammatory response included influx of leucocytes into the granuloma surrounding the tissue chamber, expression of IL-1 beta on macrophages present in the inflamed tissue and an increase in the mRNA coding for IL-1 beta and IL-6 proteins in the granuloma. The effects of three anti-inflammatory or immunosuppressive drugs, prednisolone, indomethacin and cyclosporin A, on IL-1 beta and PGE2 production in zymosan and Bordetella-pertussis-vaccine (BPV)-challenged tissue chambers were also examined. Oral treatment with prednisolone and cyclosporin A of zymosan-challenged animals showed a dose-dependent reduction of IL-1 beta concentrations, but no effect of indomethacin. Both prednisolone and indomethacin dose-dependently reduced PGE2 concentrations to control levels, while cyclosporin A was effective only at the highest dose tested (100 mg/kg/day p.o.). In drug-treated BPV-challenged animals, prednisolone and cyclosporin A also showed a dose-dependent reduction of IL-1 beta, while indomethacin was again ineffective. Prednisolone and indomethacin also dose-dependently reduced the PGE2 concentrations to control levels, whereas cyclosporin A was effective only at the highest dose tested (100 mg/kg/day p.o.). This model will be useful for investigating the mechanisms controlling the production of IL-1 beta from the mRNA level to the secretion of mature biologically active protein [1], and in the search for new drugs which could selectively interfere with this process.

Animals↗

PubMed1993

The influence of anti-rheumatic drugs on hepatic mRNA levels of acute-phase proteins in rats with adjuvant arthritis.

Using specific cDNA probes, we have investigated drug-induced changes in hepatic mRNA levels of the major acute-phase proteins (APP) fibrinogen, alpha 2-macroglobulin (alpha 2-MG), albumin and alpha 1-acid glycoprotein (alpha 1-AGP) in male Lewis rats with adjuvant arthritis. Test compounds were given orally from day 0 to 20 and hepatic mRNA analysis was performed at day 21. Prednisolone (1, 3, 10 mg/kg), Cyclosporine A (1, 3, 10 mg/kg) and cyclophosphamide (3 mg/kg) dose-dependently normalized hepatic mRNA levels of all four APP. Equipotent anti-inflammatory doses of indomethacin (0.3, 1 mg/kg) significantly downregulated alpha 2-MG mRNA levels but were much less effective in influencing albumin and alpha 1-AGP mRNA levels and even slightly increased hepatic fibrinogen mRNA levels. These results suggest that cytokine over-production, which is thought to be responsible for the acute-phase response in rats with adjuvant arthritis, can be effectively downregulated by immunosuppressive drugs, but is distinctly less affected by the cyclooxygenase inhibitor indomethacin.

Acute-Phase Proteins↗

PubMed1993

Interferon-gamma overcomes the glucocorticoid-mediated and the interleukin-4-mediated inhibition of interleukin-1 beta synthesis in human monocytes.

Interleukin-1 (IL-1) has been implicated in the tissue destruction of rheumatoid arthritis, a disease that is widely treated with glucocorticoids. In this study we investigated the effect of the T cell product interferon-gamma (IFN-gamma) on the glucocorticoid-mediated and on the IL-4-mediated inhibition of IL-1 beta mRNA and IL-1 beta protein synthesis in highly purified human monocytes. Both dexamethasone and IL-4 dose-dependently inhibited IL-1 beta mRNA and IL-1 beta protein synthesis after stimulation with LPS (300 ng/ml); maximal inhibition of 80-90% was achieved. IFN-gamma (1-100 U/ml) did not influence IL-1 beta mRNA and IL-1 beta protein levels in unstimulated cells, but potentiated the LPS-induced synthesis of IL-1 beta mRNA and IL-1 beta protein. After a preincubation time of 1 h, 100 U/ml of IFN-gamma increased the LPS-induced IL-1 beta production by about 20-40%. When human monocytes were preincubated for 1 h with IFN-gamma (100 U/ml) prior to the addition of dexamethasone (10(-6) M) and prior to the stimulation with LPS, the dexamethasone-mediated inhibition of IL-1 beta mRNA and IL-1 beta protein synthesis was totally neutralized by IFN-gamma. In addition, IFN-gamma totally overcame the negative effect of IL-4 (100 pM) on IL-1 beta protein synthesis. A preincubation period of at least 1 h with IFN-gamma was necessary for the neutralization of the dexamethasone effect. If IFN-gamma was given at the same time or after dexamethasone, only a weak effect was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Blotting, Northern↗

PubMed1992

Transforming growth factors type-beta and dexamethasone attenuate group II phospholipase A2 gene expression by interleukin-1 and forskolin in rat mesangial cells.

Treatment of rat mesangial cells with interleukin-1 beta (IL-1 beta) and forskolin induced, in a synergistic fashion, the expression of group II phospholipase A2 (PLA2) mRNA, with subsequent increased synthesis and secretion of PLA2. In contrast, interleukin-6 did not increase PLA2 mRNA levels of PLA2 activity. Transforming growth factor (TGF) beta 1, TGF beta 2 and TGF beta 3 equipotently attenuated the IL-1 beta- and forskolin-induced elevation of PLA2 mRNA, as well as PLA2 synthesis and secretion. The glucocorticoid dexamethasone only partially suppressed the IL-1 beta- and forskolin-induced elevation of PLA2 mRNA, but totally inhibited PLA2 synthesis and secretion.

Animals↗

PubMed1992

T-cell responsiveness to an oncogenic peripheral protein and spontaneous autoimmunity in transgenic mice.

Why T cells develop autoimmune reactivity to some antigens and tolerance to others is unknown. Various mechanisms can provide for T-cell tolerance. These include deletion in the thymus, exhaustive differentiation in the periphery, T-cell receptor and coreceptor downregulation, and anergy. Which mechanisms normally provide for tolerance to antigens expressed on specific tissues and why they sometimes fail is unclear. To understand this, we analyzed how a tissue-specific protein with defined timing and location of expression is recognized by T cells so as to induce tolerance or autoimmunity. We crossed mice expressing the simian virus 40 large tumor antigen on pancreatic acini beginning 4-25 days after birth with mice transgenic for a rearranged T-cell receptor that recognizes this antigen presented by the class I major histocompatibility complex molecule H-2Kk. No T-cell tolerance was found; rather, T-cell reactivity accompanied lymphocytic infiltration and pancreatic acinar destruction. This result argues that T cells may become spontaneously autoreactive to certain postnatally expressed peripheral proteins and that this reactivity may lead to autoimmune disease.

Age Factors↗

PubMed1992

Recombinant human C5a induces transcription but not translation of interleukin-1 beta mRNA in human monocytes.

The effect of recombinant human C5a (rhC5a) on the synthesis of interleukin-1 beta (IL 1 beta) was investigated in highly purified human monocytes, isolated by leukapheresis and counter-current elutriation. RhC5a induced IL 1 beta mRNA synthesis in a dose- and time-dependent manner; maximal induction was achieved at 3 h with rhC5a concentrations of 200 to 500 ng/ml. The IL 1 beta mRNA induction with rhC5a was about 75% of the response observed using lipopolysaccharide (LPS) as the stimulus (300 ng/ml). On the other hand, rhC5a in optimal concentrations only weakly stimulated IL 1 beta protein synthesis, as measured by a two-site-directed enzyme-linked immunoassay. When LPS- or C5a-stimulated RNA was used to program IL 1 beta synthesis in an in vitro translation system from rabbit reticulocytes, no difference in translational efficiency was observed. Our results indicate that, in human monocytes, two signals for IL 1 beta gene expression are necessary, one signal for transcriptional activation and a second signal to induce translation of the mRNA.

Complement C5a↗

PubMed1992

Recombinant human C5a induces transcription but not translation of interleukin 1 beta mRNA in human monocytes.

The effect of recombinant human C5a (rhC5a) on the synthesis of interleukin 1 beta (IL-1 beta) was investigated in human monocytes, isolated by leukapheresis and countercurrent elutriation. rhC5a induced IL-1 beta mRNA synthesis in a dose- and time-dependent manner. Maximal induction was achieved at 3 h with rhC5a concentrations of 200 to 500 ng/ml. The maximal rhC5a-stimulated mRNA induction was about 75% of that observed using LPS as the stimulus (300 ng/ml). The inducing activity of rhC5a could be neutralized by preincubation with a polyclonal anti-C5a antibody. On the other hand rhC5a in optimal concentrations only weakly stimulated IL-1 beta protein synthesis, as measured by a two-site directed enzyme-linked immunoassay. When compared on Northern blots, a slightly reduced mobility of C5a-stimulated IL-1 beta mRNA was observed relative to LPS-stimulated RNA. To exclude the possibility that structural defects in the IL-1 beta mRNA are responsible for the weak translational efficiency after C5a stimulation a primer extension experiment was performed. No difference in the length of the extended fragment was detected between LPS and C5a-stimulated RNA, suggesting that the 5'-regions of the RNAs are identical. When LPS- or C5a-stimulated RNA was used to program IL-1 beta synthesis in an in vitro translation system from rabbit reticulocytes, no difference in translational efficiency was observed. Our results indicate that in human monocytes two signals for IL-1 beta gene expression are necessary, a signal for transcriptional activation and another signal to induce translation of the mRNA.

Blotting, Northern↗

PubMed1991

PDGF suppresses the activation of group II phospholipase A2 gene expression by interleukin 1 and forskolin in mesangial cells.

Treatment of rat mesangial cells with interleukin 1 beta (IL-1 beta) and forskolin greatly enhanced the expression of group II phospholipase A2 (PLA2) mRNA, with subsequent increased synthesis and secretion of PLA2, as detected by PLA2 activity measurements and immunoprecipitation of culture media of [35S]methionine-labelled mesangial cells. PDGF-BB dose-dependently suppressed the IL-1 beta- and forskolin-induced elevation of PLA2 mRNA, as well as PLA2 synthesis and secretion. In contrast, PDGF-AA had no inhibitory effect. The tyrosine kinase inhibitor genistein dose-dependently antagonized the inhibitory effect of PDGF-BB on IL-1 beta-stimulated PLA2 secretion, thus suggesting that tyrosine phosphorylation may be required for PDGF-BB inhibition of PLA2 gene expression in mesangial cells.

Animals↗

PubMed1989

Interleukin-6 is the major regulator of acute phase protein synthesis in adult human hepatocytes.

The three monokines interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha), and interleukin-6 (IL-6) modulate acute phase plasma protein synthesis in adult human hepatocytes. Only IL-6 stimulates the synthesis of the full spectrum of acute phase proteins as seen in inflammatory states in humans, i.e. synthesis and secretion of C-reactive protein, serum amyloid A, fibrinogen, alpha 1-antitrypsin, alpha 1-antichymotrypsin and haptoglobin are increased while albumin, transferrin and fibronectin are decreased. IL-1 beta as well as TNF alpha, although having a moderate effect on the positive acute phase proteins and inhibiting the synthesis of fibrinogen, albumin and transferrin, fail to induce serum amyloid A and C-reactive protein. These data suggest that IL-6 plays the key role in the regulation of acute phase protein synthesis in human hepatocytes.

Acute-Phase Proteins↗

PubMed1989

Fate and biological action of human recombinant interleukin 1 beta in the rat in vivo.

The plasma half life of recombinant human interleukin 1 beta (rhIL 1 beta) was determined in rats by measuring the disappearance of the radioactivity of 125I-labeled rhIL 1 beta from the circulation. The plasma clearance showed a biphasic behavior: an initial fast disappearance (half life of about 3 min) was followed by a second slower one (half life of about 4 h). Twenty minutes after a single-dose injection of 125I-labeled rhIL 1 beta most of the radioactivity was concentrated in kidneys, liver and intestine. rhIL 1 beta induced the synthesis of alpha 1-acid glycoprotein (AGP), alpha 1-cysteine proteinase inhibitor (CPI) and beta-fibrinogen mRNA in liver. Half maximal stimulation was elicited by approximately 3000 U of rhIL 1 beta per animal. The mRNA changes for AGP and CPI were followed by corresponding protein increases in serum. Twenty hours after rhIL 1 beta injection, serum AGP rose from 0.7 to 2.5 mg/ml. CPI increased from 0.3 to 1.9 mg/ml 25 h after administration of rhIL 1 beta. Within 20 h after rhIL 1 beta injection, albumin serum concentration showed a strong decrease, preceded by a reduction in hepatic albumin mRNA levels. Neither changes in albumin synthesis nor degradation can explain this decrease suggesting that other mechanisms such as increased transvascular permeability are involved.

Acute-Phase Proteins↗

PubMed1989

An assay for the detection of interleukin-1 synthesis inhibitors: effects of antirheumatic drugs.

The monokines interleukin-1 beta and alpha (IL-1) play a central role in the connective tissue destruction of many chronic inflammatory diseases. A high capacity screening assay for the detection of inhibitors of IL-1 biosynthesis has been established. Normal human monocytes were obtained by leukapheresis and elutriation. IL-1 beta and alpha biosynthesis was stimulated with LPS, and cell-associated and secreted IL-1 beta and IL-1 alpha were measured by specific immunoassays (ELISA). The mean total IL-1 beta (cell-associated and secreted) production in 18 different donors was 11 ng/10(6) cells (range 1.2-28.8). Secreted IL-1 beta represented 31 to 86% of the total IL-1 beta. More IL-1 alpha than IL-1 beta was produced but, unlike IL-1 beta, IL-1 alpha was poorly secreted. The steroids prednisolone and dexamethasone, gold (sodium aurothiomalate) and chloroquine were potent inhibitors of the IL-1 production. Mean IC50 values of 180 nM (range 2.5 nM-1 microns), 10 microM (range 6-20 microM) and of 75 microM were found for prednisolone, gold and chloroquine, respectively. Above 5 microM, the non-steroidal anti-inflammatory compounds indomethacin and BW755C increased IL-1 beta biosynthesis. Nordihydroguaiaretic acid inhibited the level of the secreted form of IL-1 beta, but tended to increase the cell-associated level. D-Penicillamine (up to 6 mM), cyclosporin A (up to 1 microM) and methotrexate (up to 12 microM) inhibited neither cell-associated nor secreted IL-1 beta levels. This high capacity assay, which is insensitive to classical NSAIDs, may serve in the detection and characterization of new classes of anti-inflammatory compounds.

Anti-Inflammatory Agents↗

PubMed1988

Plasma clearance, organ distribution and target cells of interleukin-6/hepatocyte-stimulating factor in the rat.

The plasma half-life of recombinant human interleukin-6 (rhIL-6) was determined in rats by measuring the disappearance of the biological activity as well as of the radioactivity of 125I-rhIL-6 from the circulation. The kinetics of clearance were biphasic. It consisted of a rapid initial disappearance corresponding to a half-life of 3 min, and of a second slow one corresponding to a half-life of about 55 min. By cellulose-acetate electrophoresis it was shown that rhIL-6 binds to a plasma protein resulting in a complex migrating in the beta-gamma region; 20 min after intravenous injection, about 80% of the 125I-rhIL-6 that had disappeared from the circulation was found in the liver. 125I-rhIL-6 was exclusively localized on the surface of parenchymal cells suggesting the existence of an interleukin-6 receptor on the hepatocytes.

Animals↗

PubMed1988

Cell-free-synthesized interleukin-6 (BSF-2/IFN-beta 2) exhibits hepatocyte-stimulating activity.

Secretory products of cultured human blood monocytes contain a hepatocyte-stimulating factor which is able to induce the acute-phase proteins alpha 2-macroglobulin and fibrinogen in rat liver cells. Total RNA was isolated from unstimulated and lipopolysaccharide-stimulated human monocytes and translated in a reticulocyte lysate. The capability of the cell-free synthesized proteins to induce the acute-phase proteins alpha 2-macroglobulin and fibrinogen was assayed in rat hepatocyte primary cultures and in the rat hepatoma cell line Fao. The products translated from the mRNA of lipopolysaccharide-stimulated human monocytes induced mRNAs for alpha 2-macroglobulin and fibrinogen and therefore contain hepatocyte-stimulating factor. The translation products of unstimulated monocytes had no effect. A cDNA containing the coding sequence for interleukin-6 (B-cell stimulatory factor 2, interferon-beta 2/26-kDa protein, interleukin HP1) derived from human T-cells cloned into the transcription vector pGEM4 was transcribed in vitro. Translation of the isolated RNA in a reticulocyte lysate led to the synthesis of a protein of about 25 kDa. This cell-free synthesized interleukin-6 exhibited hepatocyte-stimulating activity measured by the induction of beta-fibrinogen mRNA in Fao cells. Using an antibody against interleukin-6, two proteins of 22 kDa and 23 kDa were immunoprecipitated from the culture medium of lipopolysaccharide-stimulated human monocytes. These two proteins were not synthesized by unstimulated monocytes. When total RNA from unstimulated human monocytes and lipopolysaccharide-stimulated human monocytes and lymphocytes was subjected to Northern analysis and hybridized with the interleukin-6 cDNA, a strong hybridization signal corresponding to an RNA of about 1300 bases was detected only in the RNA from lipopolysaccharide-stimulated human monocytes, indicating that human monocytes express the interleukin-6 gene after stimulation. The data presented in this paper strongly suggest that hepatocyte-stimulating factor from human monocytes and interleukin-6 from T-cells are identical.

Animals↗

PubMed1988

Induction of alpha 1-acid glycoprotein by recombinant human interleukin-1 in rat hepatoma cells.

The induction of alpha 1-acid glycoprotein mRNA by recombinant murine interleukin-1, recombinant human interleukin-1 alpha, and recombinant human interleukin-1 beta has been studied in the rat hepatoma cell line Fao. Whereas the stimulatory capacities of recombinant human interleukin-1 alpha and recombinant murine interleukin-1 were almost identical, the concentrations of recombinant human interleukin-1 beta needed for half-maximal induction of alpha 1-acid glycoprotein mRNA were lower by three orders of magnitude. A 60-fold increase in alpha 1-acid glycoprotein mRNA levels was observed 18 h after the addition of recombinant interleukin-1 beta. In parallel albumin mRNA levels decreased to about 30%. The alpha 1-acid glycoprotein mRNA induction was strictly dependent on the presence of dexamethasone. For a full stimulation dexamethasone concentrations of greater than 10(-7) M were needed, whereas concentrations of less than 10(-12) M were ineffective. The increase in alpha 1-acid glycoprotein mRNA after recombinant human interleukin-1 beta was followed by a 36-fold stimulation in alpha 1-acid glycoprotein synthesis and secretion. When protein synthesis was blocked by either cycloheximide, puromycin, or emetine, the induction of alpha 1-acid glycoprotein mRNA by recombinant human interleukin-1 beta was impaired suggesting the involvement of a short-lived protein in the induction of alpha 1-acid glycoprotein mRNA.

Animals↗