Biomedical subjects

F Re

Publications and source records attributed to F Re.

At least 19 recordsLinked to original sources

PubMed2006

Bone marrow mammaglobin expression as a marker of graft-versus-tumor effect after reduced-intensity allografting for advanced breast cancer.

We assessed mammaglobin (MMG) gene expression in bone marrow (BM) aspirates from patients with advanced breast cancer who had received a reduced-intensity conditioning and stem cell allografting, in order to detect a graft-versus-tumor effect on micrometastatic disease. Nine patients received a reduced-intensity conditioning with fludarabine, cyclophosphamide, and thiotepa, followed by peripheral blood allografting from HLA-identical sibling donors. Nested RT-PCR analysis with sequence-specific primers for MMG was carried out on a monthly basis on BM samples. Three patients had MMG-positive BM, four patients had MMG-negative BM before allografting, and two were undetermined. In two patients, a clinical response after allografting (partial remission) occurred concurrently with the clearance of MMG expression, at a median of 6 months after allografting, following immune manipulation. In two patients, a prolonged stable disease and negative MMG expression occurred after day +360 from allografting. In two patients, progression of the disease was associated with MMG RT-PCR changing from negative to positive. In one case, a disease response occurring after donor lymphocyte infusion and grade II acute GVHD was heralded by negativization of MMG expression. Although preliminary, these data suggest that a graft-versus-breast cancer effect is detectable on micrometastatic BM disease.

Adult↗

PubMed2005

Imiquimod and S-27609 as adjuvants of DNA vaccination in a transgenic murine model of HER2/neu-positive mammary carcinoma.

DNA vaccination against HER-2/neu is an effective way to induce an immune response able to oppose the spontaneous development of mammary tumours occurring in HER-2/neu transgenic mice. In this study, we have evaluated the potential of Imiquimod and the analogue S-27609 as adjuvants of DNA vaccination against HER-2/neu in transgenic mice. The association of a DNA vaccine encoding a portion of rat HER2/neu with either Imiquimod or S-27609 was found to delay the development of spontaneous mammary tumours and to reduce their incidence, in comparison with DNA vaccination alone. Almost 80 or 40% of tumour-free mice were found at the end of measurement time in mice vaccinated and supplemented with Imiquimod or S-27609, respectively. The antitumour preventive effect was associated with increased antibody and cell-mediated immune responsiveness against HER-2/neu. In mice vaccinated and supplemented with Imiquimod, a small but significant increase of rat p185neu-specific cytotoxicity and of IFN-gamma and IL-2-producing CD8T cells, together with a reduction of IL-4-producing CD4T cells, and a switch from an IgG1 towards a IgG2a phenotype of anti-p185neu antibodies, suggested a TH1 polarization of the immune response. The immunoregulatory efficacy of S-27609 was lower than that observed for Imiquimod. These data highlight the potential of Imiquimod, and, to a lower extent, of S-27609, as immunological adjuvants of therapeutic DNA vaccines.

Adjuvants, Immunologic↗

PubMed2003

[The role of saliva in maintaining oral health].

It is now established that saliva is important for the health of both soft and hard oral tissues. This article focuses on the role played by saliva in influencing oral structures: the most important factors related to it will be illustrated. The action of saliva and the multifunctional aspects of its components in both detrimental and beneficial effects on oral health are underlined.

Dental Plaque↗

PubMed2001

Toll-like receptor 2 (TLR2) and TLR4 differentially activate human dendritic cells.

Toll-like receptors (TLRs) mediate cell activation by various microbial products. Here, we demonstrate that activation of dendritic cells by TLR2 or TLR4 agonists, although it led to comparable activation of NF-kappa B and mitogen-activated protein kinase (MAPK) family members, resulted in striking differences in cytokine and chemokine gene transcription, suggesting that TLR2 and TLR4 signaling is not equivalent. A TLR4 agonist specifically promoted the production of the Th1-inducing cytokine interleukin (IL) 12 p70 and the chemokine interferon-gamma inducible protein (IP)-10, which is also associated to Th1 responses. In contrast, TLR2 stimulation failed to induce IL-12 p70 and interferon-gamma inducible protein (IP)-10 but resulted in the release of the IL-12 inhibitory p40 homodimer, producing conditions that are predicted to favor Th2 development. TLR2 stimulation also resulted in preferential induction of IL-8 and p19/IL-23. Involvement of phosphatidylinositol 3-kinase and p38 MAPK in the TLR-mediated induction of several cytokine and chemokine messages was demonstrated using specific inhibitors. Thus, TLRs can translate the information regarding the nature of pathogens into differences in the cytokines and chemokines produced by dendritic cells and therefore may contribute to the polarization of the acquired immune response.

Dendritic Cells↗

PubMed2000

Different immune reconstitution in multiple myeloma, chronic myeloid leukemia and acute myeloid leukemia patients after allogeneic transplantation of peripheral blood stem cells.

In this study we compared the lymphocyte reconstitution in 13 multiple myeloma (MM), nine acute myeloid leukemia (AML) and 10 chronic myeloid leukemia (CML) patients after allogeneic G-CSF-mobilized PBSC transplantation from HLA-identical siblings. Conditioning regimens included standard total body irradiation + cyclophosphamide (CY), or busulphan + CY, whereas VP-16 was added in patients with advanced disease. Overall comparable numbers of mononuclear cells, CD34+ cells and CD3+ T cells were infused in each group. A significantly higher CD3+ T cell number was observed in MM and AML than in CML patients 1 month after transplant. However, MM patients showed a faster and better recovery of CD4+ T cells than both AML and CML patients at 3 months (P = 0.01 and P = 0.01, respectively) and 12 months (P = 0.01 vs AML, while P = NS vs CML) after transplant, and had a CD4:CD8 ratio > 1 with a median CD4+ T cell value > 400/microl 1 year after transplant. Development of acute graft-versus-host disease (GVHD) did not affect CD4:CD8 ratios but patients who experienced acute GVHD > grade I had lower CD4+ and CD8+ T cell numbers at all time points. However, after excluding patients with GVHD > grade I, MM patients still showed a significantly higher CD4+ T cell value than patients with myeloproliferative diseases 1 year after transplant. These findings suggest that although allogeneic PBSC transplantation induces rapid immune reconstitution, different kinetics may occur among patients with hematological malignancies. In particular, the rapid reconstitution of CD4+ T cells in MM patients may contribute to the low transplant-related mortality achieved in this disease.

Acute Disease↗

PubMed1999

Rapid induction of CD40 on a subset of granulocyte colony-stimulating factor-mobilized CD34(+) blood cells identifies myeloid committed progenitors and permits selection of nonimmunogenic CD40(-) progenitor cells.

CD40 antigen is a costimulatory molecule highly expressed on dendritic cells (DC) and activated B cells, which induces T-cell proliferation through the binding with CD40L receptor. In this study, we evaluated CD40 expression on normal CD34(+) blood cells and functionally characterized CD34(+)CD40(+) and CD34(+)CD40(-) cell subsets. CD40, CD80, and CD86 antigens were constitutively expressed on 3.2% +/- 4.5%, 0%, and 1.8% +/- 1.2% CD34(+) blood cells, respectively. However, after 24 hours in liquid culture with medium alone, or with tumor-necrosis-factor-alpha (TNF-alpha), or with allogeneic mononuclear cells 10.8% +/- 3.8%, 75.3% +/- 15.0% and 53. 7% +/- 17.0% CD34(+) blood cells, respectively, became CD40(+). After incubation for 24 hours with TNF-alpha CD34(+)CD40(+) blood cells expressed only myeloid markers and contained less than 5% CD86(+) and CD80(+) cells. Also, a 24-hour priming with TNF-alpha or ligation of CD40 significantly increased the CD34(+) blood cells alloantigen presenting function. Finally, purified CD34(+)CD40(+) blood cells stimulated an alloreactive T-cell response in MLC, were enriched in granulocytic, monocytic, and dendritic precursors, and generated high numbers of DC in 11-14 d liquid cultures with GM-CSF, SCF, TNF-alpha and FLT-3L. In contrast, CD34(+)CD40(-) cells were poorly immunogenic, contained committed granulocytic and erythroid precursors and early progenitors, and differentiated poorly toward the DC lineage. In conclusion, a short incubation with TNF-alpha allows the selection of CD40(+) blood progenitors, which may be a useful source of DC precursors for antitumor vaccine studies, and also a CD34(+)CD40(-) blood cell fraction that could be exploited in innovative strategies of allogeneic transplantation across HLA barriers.

Adult↗

PubMed1999

Discrepancy between serological complete remission and concomitant new bone lytic lesions after infusion of escalating low doses of donor lymphocytes in multiple myeloma: a case report.

A graft-versus-myeloma effect has been previously induced by infusing high numbers of donor lymphocytes after allogeneic stem cell transplantation in relapsed/refractory multiple myeloma (MM) patients. A 43-year-old patient with MM refractory to standard chemotherapy and autologous transplantation received an allogeneic HLA-matched T cell-depleted marrow transplant from his sister after conditioning with single dose total-body irradiation, melphalan and cyclophosphamide. Twenty-four months after transplant neither a significant reduction of serum M protein nor evidence of acute or chronic graft-versus-host disease (GVHD) were observed. The patient was then treated with four escalating low doses of donor lymphocyte infusions (DLI) (0.1, 1.0, 5.0 and 5.0 x 106 CD3+ T cells/kg, respectively) over a 13 month period. Following the second infusion a mild liver acute GVHD and a partial, but transient, response occurred. After the last DLI the patient achieved a complete remission and developed extensive chronic GVHD. However, concomitant with the disappearance of clonal plasma cells from the marrow and of serum M protein, two new bone lytic lesions appeared requiring treatment with radiotherapy. In conclusion, escalating low doses of DLI may be effective in MM and may prevent severe acute but not chronic GVHD. However, the efficacy of DLI in extramedullary MM lesions is still unclear.

Adult↗

PubMed1999

Antibodies reactive with neutrophils following allogeneic haematopoietic stem cell transplantation.

Allogeneic haematopoietic stem cell transplants might induce immunological alterations leading to autoimmune-like syndromes. In particular neutrophil-associated antigens could represent the target for autoantibodies against neutrophils in patients receiving an allogeneic peripheral stem cell or bone marrow transplantation, giving rise to granulocytopenia. With this aim we studied prospectively 43 allotransplanted patients for the presence of antibodies reacting with neutrophils (ARN), looking for a correlation with a post-engraftment neutropenia. Our data showed that the direct test for ARN was positive in 30 patients. Interestingly, 7/7 patients who received a T-cell-depleted marrow transplant developed ARN. Antibodies with a specific neutrophil-antigen reactivity were detected in 4 patients, 1 with an anti-CD16/FcbetaRIIIb receptor reactivity and 3 with anti-NA 1 reacting patterns, respectively. From a clinical point of view, it was not possible to demonstrate a close and significant relationship between neutropenia and ARN, although patients showing ARN had slightly lower absolute levels of peripheral neutrophils until 6 months after BMT. In conclusion, ARN may be detected in the majority of patients following allogeneic stem cell transplantation; in addition, since ex vivo or in vivo T-cell-depletion leads to a higher percentage of patients positive for ARN, it could be hypothesized that "autoimmune-like" disorders in transplanted patients might be related to a T-cell derangement due to different numbers and subsets of T lymphocytes.

Adult↗

PubMed1998

Alloantigen presenting capacity, T cell alloreactivity and NK function of G-CSF-mobilized peripheral blood cells.

In this study we addressed whether the proportion and the function of antigen presenting cells (APC), T and NK lymphocytes are modified in the apheresis product of six healthy donors who received a stem cell mobilizing treatment with glycosylated G-CSF at 10 microg/kg/day x 5 days s.c. Flow cytometry analysis showed comparable percentages of HLA-DR+, CD19+, CD86+, CD80+ and CD1a+ cells in preG-CSF-peripheral blood mononuclear cells (preG-PBMC) and after mobilization in G-PBMC, whereas the proportion of CD14+ monocytes significantly increased in G-PBMC (3+/-1% vs 17+/-8%, P = 0.003). Analysis of lymphocyte subsets in preG-PBMC and G-PBMC showed similar proportions of CD3+, CD4+, CD8+ and CD28+ T cells, but a significantly lower percentage of CD16+ (11+/-7% vs 4+/-1%, P=0.01), CD56+ (15+/-6% vs 5+/-2%, P= 0.008), CD57+ (16+/-9% vs 5+/-2%, P=0.04), CD25+ (19+/-2% vs 9+/-6%, p=0.009) and CD122+ (5+/-2% vs 2+/-1%, P = 0.05) cells in G-PBMC. Unfractionated preG-PBMC and G-PBMC were irradiated and tested in primary mixed leukocyte culture (MLC) with two HLA-incompatible responders and induced efficient alloresponses in four of six cases, whereas G-PBMC stimulated poorly in the remaining two cases. Also, in allo-MLC with irradiated G-PBMC we detected lower amounts of IFN-gamma (P = 0.04) and of IL-2 (P = 0.06) than in allo-MLC with preG-PBMC. Furthermore, freshly isolated preG-PBMC and G-PBMC from each donor exerted comparable allogeneic responses to HLA-incompatible irradiated mononuclear cells in all cases. However, G-PBMC showed no NK activity against K562 target cells at any effector:target ratio tested. These data suggest that normal G-PBMC may prevent Thl alloresponses, maintain efficient alloreactivity to HLA mismatched antigens and have impaired NK activity.

Antigen Presentation↗

PubMed1998

ECG changes during dobutamine stress test and spontaneous recovery of contractility in patients with myocardial infarction.

UNLABELLED: Recent reports suggest a relationship between ECG changes and myocardial viability during dobutamine stress echocardiography in patients with myocardial infarction. The aim of the study was to analyze the predictive value of T-wave normalization and ST segment elevation during low- (10 mucg/Kg/m') and high-dose (40 mucg/Kg/m') dobutamine stress test for late spontaneous recovery of function in patients with a first uncomplicated Q-wave myocardial infarction. METHODS: Seventy eight consecutive patients (59 +/- 9 yrs; males = 67; anterior MI = 41, inferoposterior MI = 37 pts) underwent baseline 2D echo and dobutamine stress test at 9 +/- 2 days from onset of symptoms and they were free of cardiac events during the first three months after myocardial infarction. T-wave normalization (negative T-wave becoming > or = 1 mm upright in > or = 2 leads) and ST segment elevation (> or = 0.1 mm in > or = 2 leads) at low- and high-dose dobutamine infusion were compared with an improvement of contractility in the infarct area detected echocardiographically at three months. A wall motion score decrease in infarct area > or = 2 was the criterion for recovery of contractility. RESULTS: ST segment elevation occurred in 19/78 patients at low dose (24%) and in 45/78 patients at high dose (58%). Late recovery of contractility in the infarct area was observed in 38/78 patients (49%). The positive and negative predictive values of ST segment elevation for late recovery of contractility were, respectively, 63-56% at low dose and 47-48% at high dose. A baseline negative T-wave in > or = 2 leads was present in 56 patients, and 27 (48%) showed recovery of contractility at three months. T-wave normalization occurred in 14 patients at low-dose (25%) and in 29 patients at high-dose dobutamine infusion (52%). The positive and negative predictive values of T-wave normalization were, respectively, 71-59% at low dose and 62-67% at high dose. Both ECG markers were present in 10/56 patients at low dose and in 19 patients at high dose. The positive and negative predictive values, respectively, were 70-57% at low dose and 58-57% at high dose. At univariate analysis, neither the ECG changes alone nor their combination during dobutamine stress testing were shown to be significant predictors of recovery of function. CONCLUSIONS: Our study demonstrates that in patients with a first uncomplicated Q-wave myocardial infarction, the T-wave normalization and/or the ST segment elevation occurring during early dobutamine stress testing are not reliable predictors of late spontaneous recovery of contractility in the infarct area.

Adrenergic beta-Agonists↗

PubMed1997

HIV-1 Vpr: G2 cell cycle arrest, macrophages and nuclear transport.

HIV-1 possesses six open reading frames in addition to the gag, pol, and env shared by all retroviruses. One of these accessory genes, vpr, is required for maximal viral replication in macrophages. The molecular mechanism underlying this effect may be related to one of the unusual properties of the encoded protein: some believe Vpr promotes nuclear translocation of preintegration complexes in non-dividing cells; also, Vpr arrests the cell cycle in G2 by inhibiting an upstream activator of p34cdc2-cyclin B. Elucidation of Vpr-cell cycle interactions may provide insight into both HIV-1 and basic cell biology.

Acquired Immunodeficiency Syndrome↗

PubMed1997

Prognostic value of left ventricular volume response during dobutamine stress echocardiography.

AIMS: An abnormal left ventricular volume response during dobutamine echocardiography identified patients with severe coronary artery disease. The aim of the study was to assess the prognostic value of left ventricular volume changes during dobutamine stress echocardiography in 136 patients. METHODS AND RESULTS: Endpoints were defined as spontaneous cardiac events at follow-up. Left ventricular end-diastolic and end-systolic volume changes (abnormal response: < 10% and < 20% decrease, respectively) were compared with other clinical and stress test variables. During 18 +/- 7 months of follow-up, 31 cardiac events occurred: 12 hard events (cardiac death [n = 6], myocardial infarction [n = 6]) and 19 soft events (unstable angina [n = 16], congestive heart failure [n = 3]). End-diastolic volume response (P = 0.006), diabetes (P = 0.008), inducible wall motion abnormalities (P = 0.024), end-systolic volume response (P = 0.039) and inducible angina (P = 0.038) were related to a greater likelihood of cardiac events. The Cox regression analysis revealed end-diastolic volume response (odds ratio: 3.0; CI 1.44-6.32) and diabetes (odds ratio: 2.7; CI 1.28-5.69) to be independent predictors of spontaneous cardiac events. Diabetes (odds ratio: 4.0; CI 1.26-12.80) and < 40% baseline ejection fraction (odds ratio: 2.21; CI1.14-4.29) were independent predictors of hard events. CONCLUSION: An abnormal end-diastolic volume response during dobutamine stress echocardiography identifies patients with an unfavourable outcome; they should be considered for more accurate prognostic stratification.

Adult↗

PubMed1996

Inhibition of interleukin-1 responsiveness by type II receptor gene transfer: a surface "receptor" with anti-interleukin-1 function.

The hypothesis that the type II receptor (RII) acts as a decoy for interleukin-1 (IL-1) was tested by gene transfer in cells expressing only the type I receptor (8387 fibroblasts). RII-transfected cells showed defective responsiveness to IL-1 in terms of NFkappaB activation, cytokine gene expression and production. Blocking monoclonal antibodies against RII restored the capacity of RII-transfected cells to respond to IL-1 beta. Hence defective IL-1 responsiveness of RII-transfected cells requires surface expression of the molecule. RII-transfected cells showed normal responsiveness to TNF, which shares functional properties and elements in the signal transduction pathway with IL-1. Cells transfected with a deletion mutant of RII missing 26 of 29 amino acids of the cytoplasmic portion of the molecule showed impaired responsiveness to IL-2. Cells transfected with full-length or the cytoplasmic deletion mutant of RII released copious amounts of RII in the supernatant. However, transfected cells showed defective responsiveness to brief exposure to IL-1, in the absence of measurable released RII. These results indicate that impairment of the responsiveness to IL-1 following RII gene transfer was dependent upon surface expression of the molecule, specific for IL-1 and unaffected by truncation of the cytoplasmic portion. Thus, the type II "receptor" is a decoy surface molecule, regulated by antiinflammatory signals, whose only known function is to capture and block IL-1.

Base Sequence↗

PubMed1995

Human immunodeficiency virus type 1 Vpr arrests the cell cycle in G2 by inhibiting the activation of p34cdc2-cyclin B.

Human immunodeficiency virus type 1 (HIV-1) vpr inhibits the replication of tumor cell lines and peripheral blood mononuclear cells. Here it is demonstrated that expression of vpr, either in the context of a provirus or from an independent genetic element, induces a discrete cell cycle arrest, with cells containing 4N DNA. Low cyclin B-associated kinase activity, as well as the status of p34cdc2 and cdc25C phosphorylation, indicates that the cascade of reactions which drives the cell into mitosis has not been initiated. The phosphatase inhibitor okadaic acid releases the block, suggesting that Vpr perturbs upstream regulatorsof the G2-M transition. These studies demonstrate that HIV-1 vpr has profound effects on the cellular factors which control entry into mitosis and indicate vpr's potential contribution to the cellular pathology associated with HIV-1 infection.

Animals↗

PubMed1994

The induction of apoptosis is a common feature of the cytotoxic action of ether-linked glycerophospholipids in human leukemic cells.

The ability of 2 recent ether-lipid derivatives, aza-phospholipids BN52205 and BN52211, to induce apoptosis in different leukemia cell lines was investigated using I-octadecyl-2-methyl-rac-glycero-3- phosphocholine (ET-18-OCH3) as a positive control. HL60, K562, Molt-4 and U937 cells were exposed for 24 hr to 20 microM of drug. The 2 aza-derivatives were as cytotoxic as ET-18-OCH3: BN52205 and BN52211 selectively induced apoptotic death in HL60, Molt-4 and U937 cells, but not in the K562-resistant cell line. Around 50% of DNA was fragmented in HL60 cells after exposure to the aza-derivatives, and 34% and 20% of DNA was fragmented in Molt-4 and U937 cells respectively. Similar results were obtained when cells were exposed to ET-18-OCH3. Our data confirm that ether lipids induce apoptosis in a variety of human leukemic cells, providing a possible explanation for their selectivity and mechanism of action.

Antineoplastic Agents↗

PubMed1994

Interleukin-13 induces expression and release of interleukin-1 decoy receptor in human polymorphonuclear cells.

The aim of this study was to examine whether interleukin-13 (IL-13), a cytokine with anti-inflammatory activities, affected expression of interleukin-1 (IL-1) receptors (R) in human polymorphonuclear cells (PMN). Treatment with IL-13 augmented both type I and type II (decoy) R transcripts, with the latter being by far the most represented. The transcriptional inhibitor actinomycin D blocked the induction of IL-1 R mRNAs by IL-13. Nuclear run-off experiments demonstrated an augmented transcriptional rate of IL-1 decoy R in IL-13-treated B lymphoblastoid cells. The protein synthesis inhibitor cycloheximide blocked type I R expression but superinduced decoy R expression. IL-13 augmented the binding of radiolabeled IL-1 beta on the PMN surface with an increased number of IL-1 receptors and no change in Kd values. IL-13 induced the surface expression of IL-1 decoy R and the release by PMN of an IL-1-binding protein identified as a soluble version of the IL-1 decoy R. These results show that PMN is an important target for IL-13 and that induction of expression and release of the IL-1 decoy R, in concert with inhibition of cytokine synthesis, may represent an important mechanism by which IL-13 blocks IL-1, a central mediator of inflammatory reactions.

Blotting, Northern↗

PubMed1994

Interleukin-13 induces the production of interleukin-1 receptor antagonist (IL-1ra) and the expression of the mRNA for the intracellular (keratinocyte) form of IL-1ra in human myelomonocytic cells.

The aim of this study was to examine the expression of interleukin-1 receptor antagonist (IL-1ra) in human myelomonocytic cells treated with IL-13. IL-13 induced IL-1ra transcripts in human circulating monocytes and polymorphonuclear cells (PMN). Induction by IL-13 was not blocked, but rather superinduced, in the presence of the protein synthesis inhibitor cycloheximide. Actinomycin D blocked induction, suggesting involvement of gene transcription. The half-life of IL-1ra transcripts was prolonged by IL-13 from 1.3 hours to 4.5 hours in monocytes and to 12 hours in PMN. By reverse transcriptase-polymerase chain reaction, IL-13 was found to augment the transcripts coding for the soluble form of IL-1ra, but also to induce the expression of the intracellular (keratinocyte) form of IL-1ra, the latter being extremely low or undetectable in myelomonocytic cells. IL-13 induced production of IL-1ra in myelomonocytic cells, augmenting both cell-associated and released protein. Induction of IL-1ra by IL-13 may represent a further mechanism by which this molecule can counteract the potent proinflammatory properties of IL-1.

Cells, Cultured↗

PubMed1994

The type II "receptor" as a decoy target for interleukin 1 in polymorphonuclear leukocytes: characterization of induction by dexamethasone and ligand binding properties of the released decoy receptor.

Whereas the signaling function of the interleukin 1 (IL-1) receptor type I (IL-1R I) has been well documented, the type II "receptor" has been suggested to act as a decoy target for this cytokine. Since IL-1 may represent a key target of the immunomodulatory and antiinflammatory properties of glucocorticoids (GC), the aim of this study was to investigate the effects of dexamethasone (Dex) on IL-1R expression in human polymorphonuclear leukocytes (PMN), which express predominantly the type II molecule (IL-1R II). We found that Dex augments the levels of steady state transcripts encoding the IL-1R I and, most prominently, those of IL-1R II. Dex induced both transcripts via transcription-dependent mechanisms and by prolongation of the mRNAs half-lives. Inhibition of protein synthesis superinduced basal and Dex-augmented IL-1R II mRNA, whereas it completely inhibited the induction by Dex of IL-1R I transcripts. Induction of IL-1R II mRNA by Dex was associated with augmented membrane expression and release of the type II IL-1 binding molecule. This effect was mediated by the GC receptor. Other steroids (17 beta-estradiol, progesterone, and testosterone) were ineffective. The concentrations of IL-1 alpha and IL-1 receptor antagonist required to displace the binding of IL-1 beta to the soluble form of the decoy molecule induced by Dex from PMN were, respectively, 100 and 2 times higher compared with IL-1 beta. The induction by Dex of the type II receptor, a decoy molecule for IL-1, may contribute to the immunosuppressive and antiinflammatory activities of Dex.

Dexamethasone↗